Ado-trastuzumab emtansine

Name: Ado-trastuzumab emtansine

Why is this medication prescribed?

Ado-trastuzumab emtansine injection is used to treat a certain type of breast cancer that has spread to other parts of the body and has not improved or has worsened after treatment with other medications. Ado-trastuzumab emtansine is in a class of medications called antibody-drug conjugates. It works by killing cancer cells.

What special precautions should I follow?

Before receiving ado-trastuzumab emtansine,

  • tell your doctor and pharmacist if you are allergic to ado-trastuzumab emtansine, trastuzumab, any other medications, or any of the ingredients in ado-trastuzumab emtansine injection. Ask your doctor or pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: apixaban (Eliquis), aspirin (Durlaza, in Aggrenox, others), atazanavir (Reyataz, in Evotaz), cilostazol (Pletal), clarithromycin (Biaxin, in Prevpac), clopidogrel (Plavix), dabigatran (Pradaxa), dalteparin (Fragmin), dipyridamole (Persantine, in Aggrenox), edoxaban (Savaysa), enoxaparin (Lovenox), fondaparinux (Arixtra), heparin, indinavir (Crixivan), itraconazole (Onmel, Sporanox), ketoconazole, nefazodone, nelfinavir (Viracept), prasugrel (Effient), ritonavir (Norvir, in Kaletra, Technivie, Viekira Pak), rivaroxaban (Xarelto), saquinavir (Invirase), telithromycin (Ketek), ticagrelor (Brilinta), vorapaxar (Zontivity), voriconazole (Vfend), and warfarin (Coumadin, Jantoven). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you are of Asian descent, or if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section, trouble breathing, even when resting, or any other medical condition.
  • tell your doctor if you are breast-feeding. You should not breast-feed while receiving ado-trastuzumab emtansine injection and for 7 months after your final dose.

Ado-trastuzumab emtansine side effects

Some side effects may occur during the injection. Tell your caregiver right away if you feel cold, light-headed, feverish or sweaty, or have chest tightness, rapid heartbeats, or trouble breathing.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Ado-trastuzumab emtansine can harm your liver. Call your doctor at once if you have signs of liver problems--upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Also call your doctor at once if you have:

  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

  • bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

  • sudden severe headache, confusion, severe drowsiness, sudden numbness or weakness on one side of the body;

  • problems with walking, breathing, speech, swallowing, or eye movement;

  • sudden chest pain or discomfort, wheezing, dry cough, feeling short of breath;

  • swelling, rapid weight gain, severe dizziness;

  • numbness or tingling in your hands or feet;

  • pounding heartbeats or fluttering in your chest; or

  • low white blood cell counts--fever, swollen gums, painful mouth sores, pain when swallowing, skin sores, cold or flu symptoms, cough, trouble breathing.

Common side effects may include:

  • easy bruising or bleeding;

  • nausea, constipation;

  • joint or muscle pain;

  • headache, tired feeling; or

  • abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Introduction

Antineoplastic agent; an anti-human epidermal growth factor receptor type 2 (anti-HER2) antibody conjugated with the microtubule inhibitor DM1 (a maytansine derivative).1 2 3 4 8 9 10 11

Stability

Storage

Parenteral

Powder for Injection

2–8°C before reconstitution.1 Do not freeze or shake.1

Use reconstituted solution immediately.1 If not used immediately, may store reconstituted drug at 2–8°C for up to 24 hours.1 Do not freeze.1

Use diluted solution immediately.1 If not used immediately, may store diluted infusion solution at 2–8°C for up to 24 hours.1 Do notfreeze or shake.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible1

Sodium chloride 0.9%

Incompatible1

Dextrose 5% in water

Advice to Patients

  • Risk of fetal harm.1 Necessity of advising women of childbearing potential to use effective contraception during therapy and for 6 months after discontinuance of drug.1 Encourage women exposed to drug during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 800-690-6720.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of discontinuing breast-feeding during therapy.1

  • Risk of severe hepatotoxicity.1 Importance of informing clinician if manifestations of acute hepatitis (e.g., nausea, vomiting, abdominal pain [particularly in the right upper quadrant], jaundice, dark urine, generalized pruritus, anorexia) occur.1

  • Importance of informing clinician if new-onset or worsening shortness of breath, cough, swelling of ankles or legs, palpitations, weight gain >5 pounds in 24 hours, dizziness, or loss of consciousness occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Uses of Ado-Trastuzumab Emtansine

  • It is used to treat breast cancer.

Uses of Ado-trastuzumab Emtansine

Ado-trastuzumab emtansine is a prescription medication used to treat a certain type of breast cancer. It used when the cancer has spread to other parts of the body and has not improved or has worsened after treatment with other medications.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.
 

Ado-trastuzumab Emtansine Interactions

Ado-trastuzumab emtansine should be taken with caution with certain other medications that can change the way it is metabolized. Let your doctor know about other medications including supplements you may be taking before starting ado-trastuzumab emtansine. Medications that interact with ado-trastuzumab include:

  • Ketoconazole
  • Itraconazole
  • Telithromycin
  • Clarithromycin
  • Ritonavir
  • Indinavir
  • Nelfinavir
  • Salquinavir
  • Nefazdone
  • Chloramphenicol
  • Clozapine

This is not a complete list of interactions with ado-trastuzumab emtasine. 

Ado-trastuzumab Emtansine Overdose

Since this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.
 

Contraindications

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

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

Administration

Check label to ensure appropriate product is being administered (ado-trastuzumab emtansine [US] or trastuzumab emtansine [Canada] and conventional trastuzumab are different products and are NOT interchangeable).

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 nonprotein adsorptive 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.

May be a vesicant; 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). 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.

Adverse Reactions

>10%:

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

Dermatologic: Skin rash (12%)

Endocrine & metabolic: Decreased serum potassium (33%; grade 3: 3%)

Gastrointestinal: Nausea (40%), constipation (27%), diarrhea (24%), abdominal pain (19%), vomiting (19%), xerostomia (17%), stomatitis (14%)

Hematologic & oncologic: Decreased platelet count (83% [nadir by day 8]; grade 3: 14%; grade 4: 3%), decreased hemoglobin (60%; grade 3: 4%; grade 4: 1%), decreased neutrophils (39%; grade 3: 3%; grade 4: <1%), hemorrhage (32%; grades 3/4: 2%), thrombocytopenia (31%; grades 3/4: 15%; Asians grades 3/4: 45%), anemia (14%; grades 3/4: 4%)

Hepatic: Increased serum AST (98%; grades 3/4: <8%), increased serum ALT (82%; grades 3/4: <6%), increased serum transaminases (29%), increased serum bilirubin (17%)

Neuromuscular & skeletal: Musculoskeletal pain (36%), arthralgia (19%), weakness (18%), myalgia (14%)

Respiratory: Epistaxis (23%), cough (18%), dyspnea (12%)

Miscellaneous: Fever (19%)

1% to 10%:

Cardiovascular: Peripheral edema (7%), hypertension (5%; grades 3/4: 1%), left ventricular dysfunction (2%; grades 3/4: <1%)

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

Dermatologic: Pruritus (6%)

Endocrine & metabolic: Hypokalemia (10%; grades 3/4: 3%)

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

Genitourinary: Urinary tract infection (9%)

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

Hepatic: Increased serum alkaline phosphatase (5%)

Hypersensitivity: Hypersensitivity (2%)

Immunologic: Antibody development (5%)

Ophthalmic: Blurred vision (5%), conjunctivitis (4%), dry eye syndrome (4%), increased lacrimation (3%)

Respiratory: Pneumonitis (≤1%)

Miscellaneous: Infusion related reaction (1%)

<1% (Limited to important or life-threatening): Anaphylactoid reaction, hepatic encephalopathy, hepatotoxicity, idiopathic noncirrhotic portal hypertension (including nodular regenerative hyperplasia), portal hypertension

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dry mouth, change in taste, abdominal pain, nausea, vomiting, diarrhea, constipation, muscle pain, joint pain, headache, nosebleed, dizziness, mouth irritation, insomnia, or rash. Have patient report immediately to prescriber signs of infusion reaction, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; 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), burning or numbness feeling, severe injection site pain, burning, edema, or irritation, severe loss of strength and energy, swelling of arms or legs, signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal headache), or signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Ado-trastuzumab emtansine Pregnancy Warnings

FDA pregnancy category: D Use of ado-trastuzumab emtansine is not recommended. Comments: Patients should be advised to use effective contraception during treatment and for 6 months following the last dose of ado-trastuzumab emtansine.

There are no adequate and well-controlled studies of ado-trastuzumab emtansine in pregnant women. Use of trastuzumab, the antibody component of ado-trastuzumab emtansine, during pregnancy has resulted in oligohydramnios, associated with fatal pulmonary hypoplasia, skeletal abnormalities and neonatal death. DM1, the cytotoxic component of ado-trastuzumab emtansine, can be expected to cause embryofetal toxicity based on its mechanism of action. If a patient is exposed to ado-trastuzumab emtansine during pregnancy apprise the patient of the potential hazard to the fetus, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-2555 and encourage the patient to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720. FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

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