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Ado-Trastuzumab Emtansine

Medically reviewed by Drugs.com. Last updated on Sep 25, 2020.

Pronunciation

(a do tras TU zoo mab em TAN seen)

Index Terms

  • Ado Trastuzumab
  • Adotrastuzumab
  • T-DM1
  • Trastuzumab Emtansine
  • Trastuzumab-DM1
  • Trastuzumab-MCC-DM1

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Kadcyla: 100 mg (1 ea); 160 mg (1 ea)

Brand Names: U.S.

  • Kadcyla

Pharmacologic Category

  • Antineoplastic Agent, Anti-HER2
  • Antineoplastic Agent, Antibody Drug Conjugate
  • Antineoplastic Agent, Antimicrotubular
  • Antineoplastic Agent, Monoclonal Antibody

Pharmacology

Ado-trastuzumab emtansine is a HER2-antibody drug conjugate which incorporates the HER2 targeted actions of trastuzumab with the microtubule inhibitor DM1 (a maytansine derivative). The conjugate, which is linked via a stable thioether linker, allows for selective delivery into HER2 overexpressing cells, resulting in cell cycle arrest and apoptosis.

Distribution

Vd: 3.13 L

Metabolism

DM1 undergoes hepatic metabolism via CYP3A4/5

Time to Peak

Near the end of the infusion

Half-Life Elimination

~4 days

Protein Binding

DM1: 93%

Special Populations: Hepatic Function Impairment

Systemic exposure (AUC) was ~38% and ~67% lower in patients with mild (Child-Pugh class A) and moderate (Child-Pugh class B) impairment, respectively, compared to patients with normal hepatic function during cycles 1 and 2 of a 3.6 mg/kg ado-trastuzumab dose.

Use: Labeled Indications

Breast cancer, early: Treatment (single agent) of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in patients with residual invasive disease following neoadjuvant taxane and trastuzumab-based treatment.

Breast cancer, metastatic: Treatment (single agent) of HER2-positive, metastatic breast cancer in patients who previously received trastuzumab and a taxane, separately or in combination, and have either received prior therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy.

Limitations of use: Patients should be selected for therapy based on an approved companion diagnostic test for HER2 protein overexpression or HER2 gene amplification in tumor specimens.

Contraindications

US labeling: There are no contraindications listed in the manufacturer's labeling.

Canadian labeling: Hypersensitivity to trastuzumab emtansine or any component of the formulation.

Dosing: Adult

Note: Do not substitute ado-trastuzumab emtansine (United States) or trastuzumab emtansine (Canada) for or with fam-trastuzumab deruxtecan, conventional trastuzumab, trastuzumab/hyaluronidase, or pertuzumab/trastuzumab/hyaluronidase; products are different and are NOT interchangeable.

Breast cancer, early, HER2+, adjuvant therapy for residual disease: IV: 3.6 mg/kg every 3 weeks for a total of 14 cycles in the absence of disease recurrence or unacceptable toxicity (von Minckwitz 2019); Maximum dose: 3.6 mg/kg.

Breast cancer, metastatic, HER2+: IV: 3.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity (Diéras 2017; Verma 2012); Maximum dose: 3.6 mg/kg.

Missed or delayed doses: If a planned dose is missed or delayed, administer as soon as possible (at the dose and rate most recently tolerated), do not wait until the next planned cycle. Then adjust schedule to maintain a 3-week interval between doses.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Note: After a dose reduction is implemented, do not re-escalate dose.

Infusion-related reaction: Slow infusion rate or interrupt infusion. Permanently discontinue if life-threatening infusion reactions occur.

Dose levels for dosage reductions and/or discontinuation:

Starting dose: 3.6 mg/kg

First dose reduction: Reduce dose to 3 mg/kg

Second dose reduction: Reduce dose to 2.4 mg/kg

Further reductions necessary: Discontinue treatment.

Hematologic toxicity:

Early breast cancer: Grades 2 to 3 thrombocytopenia (platelets 25,000/mm3 to <75,000/mm3) on scheduled day of treatment: Withhold treatment until platelet count recovers to ≤ grade 1 (platelets ≥75,000/mm3), then resume treatment at the same dose level. If two dosage delays are required, consider reducing by one dose level.

Metastatic breast cancer: Grade 3 thrombocytopenia (platelets 25,000/mm3 to <50,000/mm3): Withhold treatment until platelet count recovers to ≤ grade 1 (platelets ≥75,000/mm3), then resume treatment at the same dose level.

Grade 4 thrombocytopenia (platelets <25,000/mm3 at any time): Early or metastatic breast cancer: Withhold treatment until platelet count recovers to ≤ grade 1 (platelets ≥75,000/mm3), then resume treatment with one dose level reduction.

Cardiotoxicity:

Early breast cancer:

LVEF ≥50%: Continue treatment.

LVEF 45% to <50% and decrease is <10% points from baseline: Continue treatment and repeat LVEF assessment within 3 weeks.

LVEF 45% to <50% and decrease is ≥10% points from baseline: Withhold treatment and repeat LVEF assessment within 3 weeks; if repeat LVEF remains <50% and has not recovered to <10% points from baseline, discontinue treatment.

LVEF <45%: Withhold treatment and repeat LVEF assessment within 3 weeks; if repeat LVEF is confirmed <45%, discontinue treatment.

Symptomatic heart failure, grade 3 to 4 left ventricular systolic dysfunction, grade 3 to 4 heart failure, or grade 2 heart failure with LVEF <45%: Discontinue treatment.

Metastatic breast cancer:

LVEF >45%: Continue treatment.

LVEF 40% to ≤45% and decrease is <10% points from baseline: Continue treatment and repeat LVEF assessment within 3 weeks.

LVEF 40% to ≤45% and decrease is ≥10% points from baseline: Withhold treatment and repeat LVEF assessment within 3 weeks; if repeat LVEF has not recovered to within 10% points from baseline, discontinue treatment.

LVEF <40%: Withhold treatment and repeat LVEF assessment within 3 weeks; if repeat LVEF is confirmed <40%, discontinue treatment.

Symptomatic heart failure: Discontinue treatment.

Peripheral neuropathy, grade 3 or 4: Temporarily discontinue until resolves to ≤ grade 2.

Pulmonary toxicity: Interstitial lung disease or pneumonitis: Permanently discontinue.

Radiation therapy-related pneumonitis (adjuvant setting):

Grade 2: Discontinue ado-trastuzumab emtansine if not resolving with standard treatment.

Grade 3 or 4: Discontinue ado-trastuzumab emtansine.

Reconstitution

Check vial labels to assure appropriate product is being reconstituted (ado-trastuzumab emtansine and fam-trastuzumab deruxtecan, conventional trastuzumab, trastuzumab/hyaluronidase, or pertuzumab/trastuzumab/hyaluronidase are different products and are NOT interchangeable).

Slowly inject sterile water for injection into the vial (5 mL for 100 mg vial or 8 mL for 160 mg vial) to a reconstituted concentration of 20 mg/mL. Gently swirl vial until completely dissolved; do not shake. Reconstituted solution will be clear or slightly opalescent (there should be no visible particles) and colorless to pale brown. Dilute for infusion by adding to 250 mL sodium chloride 0.9% (do not use D5W); gently invert bag to mix (do not shake).

Administration

IV: Infuse over 90 minutes (first infusion) or over 30 minutes (subsequent infusions if prior infusions were well tolerated) through a 0.2- or 0.22-micron inline polyethersulfone filter. Do not administer IV push or bolus. Do not administer with other medications.

Monitor patient during infusion for signs of infusion-related reactions (eg, fever, chills); monitor for at least 90 minutes following initial infusion and (if tolerated) for at least 30 minutes following subsequent infusions.

Check label to ensure appropriate product is being administered (ado-trastuzumab emtansine [United States] or trastuzumab emtansine [Canada] and fam-trastuzumab deruxtecan, conventional trastuzumab, trastuzumab/hyaluronidase, or pertuzumab/trastuzumab/hyaluronidase are different products and are NOT interchangeable).

Irritant with vesicant-like properties; avoid extravasation. Ensure proper needle or catheter position prior to administration. Closely monitor infusion site during administration.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze or shake intact vials, reconstituted solution, or solutions diluted for infusion. Reconstituted vials do not contain preservative and should be used immediately, although may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F); discard after 24 hours. Solutions diluted for infusion in NS should be used immediately, although may be stored at 2°C to 8°C (36°F to 46°F) for up to 24 hours prior to use. This storage time is additional to the time allowed for the reconstituted vials.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Anthracyclines: Ado-Trastuzumab Emtansine may enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Fatigue (36% to 50%), headache (28%), peripheral neuropathy (21% to 28%; grades 3/4: 2%), insomnia (12% to 14%)

Dermatologic: Skin rash (1% to 12%)

Gastrointestinal: Nausea (40% to 42%), constipation (17% to 27%), diarrhea (12% to 24%), vomiting (15% to 19%), abdominal pain (11% to 19%), xerostomia (14% to 17%), stomatitis (14% to 15%; grades 3/4: <1%)

Hematologic & oncologic: Hemorrhage (29% to 32%; grades 3/4: ≤2%), thrombocytopenia (29% to 31%; grades 3/4: 6% to 15%; Asian patients, grades 3/4: 19% to 45%), anemia (10% to 14%; grades 3/4: 1% to 4%)

Hepatic: Increased serum aspartate aminotransferase (79% to 98%), increased serum alanine aminotransferase (55% to 82%), increased serum transaminases (29% to 32%), increased serum bilirubin (7% to 17%)

Neuromuscular & skeletal: Musculoskeletal pain (30% to 36%), arthralgia (19% to 26%), asthenia (≤18%), myalgia (14% to 15%)

Respiratory: Epistaxis (22% to 23%), cough (14% to 18%), dyspnea (8% to 12%)

Miscellaneous: Fever (10% to 19%)

1% to 10%:

Cardiovascular: Peripheral edema (4% to 7%), hypertension (5% to 6%), left ventricular dysfunction (2% to 3%)

Central nervous system: Dizziness (10%), chills (5% to 8%)

Dermatologic: Pruritus (6% to 7%)

Endocrine & metabolic: Hypokalemia (7% to 10%)

Gastrointestinal: Dyspepsia (4% to 9%), dysgeusia (8%)

Genitourinary: Urinary tract infection (9% to 10%)

Hematologic & oncologic: Neutropenia (7% to 8%; grades 3/4: 2%)

Hepatic: Increased serum alkaline phosphatase (5% to 8%)

Hypersensitivity: Hypersensitivity reaction (2% to 3%)

Immunologic: Antibody development (4% to 6%; neutralizing: 1% to 3%)

Ophthalmic: Increased lacrimation (3% to 6%), blurred vision (4% to 5%), dry eye syndrome (4% to 5%), conjunctivitis (4%)

Respiratory: Radiation pneumonitis (2%), pneumonitis (≤1%)

Miscellaneous: Infusion related reaction (1% to 2%)

Frequency not defined:

Cardiovascular: Decreased left ventricular ejection fraction

Hepatic: Hepatic encephalopathy, hepatic failure, hepatotoxicity

Respiratory: Acute respiratory distress syndrome, interstitial pulmonary disease

<1%: Nonimmune anaphylaxis, portal hypertension (including nodular regenerative hyperplasia), tumor lysis syndrome

ALERT: U.S. Boxed Warning

Hepatotoxicity:

Serious hepatotoxicity has been reported, including liver failure and death in patients treated with ado-trastuzumab emtansine. Monitor serum transaminases and bilirubin prior to initiation of ado-trastuzumab emtansine treatment and prior to each ado-trastuzumab emtansine dose. Reduce the dose or discontinue ado-trastuzumab emtansine as appropriate in cases of increased serum transaminases or total bilirubin.

Cardiotoxicity:

Ado-trastuzumab emtansine administration may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate left ventricular function in all patients prior to and during treatment with ado-trastuzumab emtansine. Withhold treatment for a clinically significant decrease in left ventricular function.

Pregnancy:

Exposure to ado-trastuzumab emtansine during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Thrombocytopenia may occur (nadir achieved by day 8; generally resolves to ≤ grade 1 by the next scheduled dose), including grade 3 or higher thrombocytopenia. The incidence of thrombocytopenia was higher in patients of Asian ancestry. Monitor platelet count at baseline and prior to each dose. May require treatment interruption or dose reduction. Monitor closely if at bleeding risk due to thrombocytopenia and/or concomitant anticoagulant use. Has not been studied in patients with platelets <100,000/mm3 prior to treatment initiation. Neutropenia and anemia have also occurred.

• Cardiotoxicity: [US Boxed Warning]: May result in left ventricular ejection fraction (LVEF) reductions. Evaluate left ventricular function (in all patients) prior to and during (eg, every 3 months) treatment; withhold for clinically significant left ventricular function decreases. Serious cases of heart failure have been observed. Treatment interruption, dosage reductions, and/or discontinuation may be required in patients who develop decreased LVEF. Use has not been studied in patients with LVEF <50%, with a history of symptomatic CHF, serious arrhythmia, or recent history (within 6 months) of myocardial infarction, or unstable angina.

• Extravasation reactions: Irritant with vesicant-like properties; avoid extravasation. Local reactions (erythema, irritation, pain, swelling, or tenderness) secondary to extravasation have been noted. These were generally mild and typically occurred within 24 hours of infusion. There is a case report of skin necrosis (delayed) following extravasation (Shafaee 2017). Monitor infusion site during infusion for possible infiltration.

• Hemorrhage: Hemorrhagic events, including central nervous system, respiratory, and gastrointestinal hemorrhage, have been observed; some hemorrhages were fatal. Some events occurred in patients who were receiving anticoagulation or antiplatelet therapy, or in patients with thrombocytopenia, although bleeding also occurred in patients without additional risk factors. Use caution when administering with antiplatelet agents or anticoagulants; consider additional monitoring when indicated.

• Hepatotoxicity: [US Boxed Warning]: Serious hepatotoxicity, including liver failure and death, has been reported. Monitor serum transaminases and bilirubin at baseline and prior to each dose. Increases (transaminases or total bilirubin) may require dose reductions or discontinuation. Hepatotoxicity is typically manifested by asymptomatic and transient increases in transaminases, although fatal cases of severe drug-induced liver injury and associated hepatic encephalopathy have occurred; may be confounded by comorbidities or concomitant hepatotoxic medications. All fatal cases occurred in patients with metastatic breast cancer. Use with caution in patients with known active hepatic disease (eg, hepatitis B or C virus). Cases of nodular regenerative hyperplasia (NRH), a rare liver disorder characterized by widespread benign transformation of hepatic parenchyma into small regenerative nodules, have been observed (by biopsy). NRH may lead to noncirrhotic portal hypertension. Consider NRH in patients with clinical symptoms of portal hypertension and/or cirrhosis-like pattern seen on liver CT scan, although without associated transaminase elevations or other manifestations of cirrhosis. Diagnosis of NRH is confirmed only by histopathology; permanently discontinue if histopathology confirms NRH.

• Hypersensitivity/infusion-related reactions: Infusion reactions (flushing, chills, fever, bronchospasm, dyspnea, wheezing, hypotension, and/or tachycardia) have been reported. After termination of infusion, these reactions generally resolved within several hours to a day. Medications for the treatment of reactions should be available for immediate use. Monitor closely for infusion reactions, especially during initial infusion (monitor during infusion and for 90 minutes after the initial infusion, and then for 30 minutes after subsequent infusions). If reaction occurs, decrease infusion rate; for severe infusion reactions, interrupt infusion; permanently discontinue for life-threatening reactions. Serious allergic/anaphylactic reaction was observed (rare). Use is not recommended in patients who had trastuzumab permanently discontinued due to infusion reaction or hypersensitivity (has not been evaluated).

• Peripheral neuropathy: Sensory peripheral neuropathy has been reported, usually grade 1, although grade 3 or higher peripheral neuropathy was also described. In the adjuvant setting, sensory and motor neuropathy were observed, with nearly one-third of cases not yet resolved at study analysis. Monitor for signs and symptoms of neuropathy. May require treatment interruption and/or dose reduction.

• Pulmonary toxicity: Interstitial lung disease (ILD), including pneumonitis has been reported; some cases resulted in acute respiratory distress syndrome and/or fatalities. Grade 3 pneumonitis has occurred. Permanently discontinue with diagnosis of ILD or pneumonitis. Signs and symptoms of pneumonitis include dyspnea, cough, fatigue, and pulmonary infiltrates. Radiation pneumonitis has been reported, including grade 3 toxicity. In the adjuvant setting, discontinue ado-trastuzumab emtansine permanently for grade 3 or higher (or grade 2 that is unresponsive to standard treatment) radiation pneumonitis. Patients with dyspnea at rest due to complications of advanced malignancy, comorbidities, or concurrent pulmonary radiation therapy may be at increased risk for pulmonary toxicity.

Concurrent drug therapy issues:

• Drug-drug/drug-food interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Asian ancestry: The incidence of thrombocytopenia was higher in patients of Asian ancestry.

• Pregnancy: [US Boxed Warning]: Exposure to ado-trastuzumab emtansine during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Dosage form specific issues:

• Do not interchange: Ado-trastuzumab emtansine and conventional trastuzumab are NOT interchangeable. Do not substitute. Ado-trastuzumab emtansine is also not interchangeable with fam-trastuzumab deruxtecan, trastuzumab/hyaluronidase, or pertuzumab/trastuzumab/hyaluronidase. Dosing and treatment schedules between ado-trastuzumab emtansine (Kadcyla) and fam-trastuzumab deruxtecan (Enhertu), conventional trastuzumab (Herceptin or trastuzumab biosimilars), trastuzumab/hyaluronidase (Herceptin Hylecta), or pertuzumab/trastuzumab/hyaluronidase (Phesgo) are different; confusion between the products may potentially cause harm to the patient. In Canada, the generic name for Kadcyla is trastuzumab emtansine (without the Ado- prefix) and may be confused with conventional trastuzumab. Verify product label prior to reconstitution and administration to prevent medication errors.

Other warnings/precautions:

• Human epidermal growth factor receptor 2 expression: Patients should be selected for therapy based on an approved companion diagnostic test for human epidermal growth factor receptor 2 (HER2) protein overexpression or HER2 gene amplification in tumor specimens. HER2 testing should be conducted using tests specific for breast cancers and by labs with demonstrated proficiency. Information on approved tests for HER2 testing is available at http://www.fda.gov/CompanionDiagnostics. Improper assay performance (including sub-optimally fixed tissue), failure to use specific reagents, deviation form assay instructions, and failure to include appropriate assay validation controls may lead to unreliable results.

Monitoring Parameters

HER2 expression status; platelet count (at baseline and prior to each dose), transaminases and bilirubin (at baseline and prior to each dose); verify pregnancy status (prior to treatment initiation in females of reproductive potential). Evaluate left ventricular function (prior to and at least every 3 months during treatment; more frequently for decreased LVEF). Monitor infusion site during infusion for possible infiltration; monitor for infusion reactions (during infusion and for 90 minutes after initial infusion and for 30 minutes after subsequent infusions); signs and symptoms of bleeding, neuropathy, and/or pulmonary toxicity

Reproductive Considerations

[US Boxed Warning]: Exposure to ado-trastuzumab emtansine during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Evaluate pregnancy status prior to treatment in females of reproductive potential; effective contraception should be used during therapy and for 7 months after the last dose of ado-trastuzumab emtansine. Males with female partners of reproductive potential should use effective contraception during therapy and for 4 months after the last dose.

Pregnancy Considerations

[US Boxed Warning]: Exposure to ado-trastuzumab emtansine during pregnancy can result in embryo-fetal harm. Advise patients of these risks.

Oligohydramnios and oligohydramnios sequence (manifested as pulmonary hypoplasia, skeletal malformations, and neonatal death) were observed following trastuzumab exposure during pregnancy (trastuzumab is the antibody component of ado-trastuzumab emtansine). Monitor for oligohydramnios if trastuzumab exposure occurs during pregnancy or within 7 months prior to conception; conduct appropriate fetal testing if oligohydramnios occurs. Based on the mechanism of action, the DM1 component of the ado-trastuzumab emtansine formulation may also cause fetal harm if administered during pregnancy.

European Society for Medical Oncology guidelines for cancer during pregnancy recommend delaying treatment with HER-2 targeted agents until after delivery in pregnant patients with HER-2 positive disease (Peccatori 2013).

Data collection to monitor pregnancy and infant outcomes following exposure to ado-trastuzumab emtansine is ongoing. If ado-trastuzumab emtansine exposure occurs during pregnancy or within 7 months prior to conception, healthcare providers should report the exposure to the Genentech (888-835-2555).

Patient Education

What is this drug used for?

• It is used to treat breast cancer.

Frequently reported side effects of this drug:

• Headache

• Dry mouth

• Stomach pain

• Heartburn

• Feeling dizzy, tired, or weak

• Upset stomach

• Throwing up

• Diarrhea

• Constipation

• Muscle pain

• Joint pain

• Nosebleed

• Mouth irritation or mouth sores

• Trouble sleeping

• Rash

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infusion reaction

• Liver problems like dark urine, feeling tired, not hungry, upset stomach, stomach pain, light-colored stools, throwing up, or yellow skin

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, a heartbeat that does not feel normal, weight gain of more than 5 pounds in 24 hours, dizziness, or passing out

• Infection

• Bleeding like throwing up blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower stomach pain, or pelvic pain

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Burning or numbness feeling

• Severe injection site redness, burning, pain, swelling, or leaking of fluid

• Feeling very tired or weak

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal headache

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.