Ado-trastuzumab emtansine

Name: Ado-trastuzumab emtansine

What should I discuss with my healthcare provider before receiving ado-trastuzumab emtansine?

You should not use ado-trastuzumab emtansine if you are allergic to it, or if you are pregnant.

To make sure ado-trastuzumab emtansine is safe for you, tell your doctor if you have:

  • liver disease;

  • bleeding or blood clotting disorder such as hemophilia; or

  • asthma, chronic obstructive pulmonary disease (COPD), sleep apnea, or other breathing disorder.

Do not use ado-trastuzumab emtansine if you are pregnant. It could harm the unborn baby or cause birth defects. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 7 months after your last dose.

You may need to have a negative pregnancy test before starting this treatment. Tell your doctor if you become pregnant during treatment.

It is not known whether ado-trastuzumab emtansine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

How is ado-trastuzumab emtansine given?

Before you receive this medicine, your doctor will perform blood tests to make sure ado-trastuzumab emtansine is the right medication to treat your cancer.

Ado-trastuzumab emtansine is injected into a vein through an IV. A healthcare provider will give you this injection.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when ado-trastuzumab emtansine is injected.

Ado-trastuzumab emtansine is usually given once every 3 weeks until your body no longer responds to the medication. Your doctor will determine how long to treat you with ado-trastuzumab emtansine.

You may need frequent medical tests at your doctor's office to be sure this medication is not causing harmful effects. Your cancer treatments may be delayed based on the results of these tests.

What should I avoid while taking ado-trastuzumab emtansine?

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Interactions for Ado-Trastuzumab Emtansine

DM1 component of ado-trastuzumab emtansine metabolized principally by CYP3A4 and, to a lesser extent, by CYP3A5.1 6

DM1 does not inhibit or induce major CYP isoenzymes in vitro.1

Substrate of P-glycoprotein (P-gp) in vitro.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Possible pharmacokinetic interaction (increased systemic exposure of DM1).1 Avoid concomitant use; select an alternative agent with no or minimal enzyme inhibition potential.1

If the potent CYP3A4 inhibitor can be discontinued, delay initiation of ado-trastuzumab emtansine therapy (until after approximately 3 elimination half-lives of the CYP3A4 inhibitor).1 If concomitant use cannot be avoided, closely monitor patients for adverse effects.1 (See Specific Drugs under Interactions.)

Specific Drugs

Drug

Interaction

Comments

Antifungals, azoles (e.g., itraconazole, ketoconazole, voriconazole)

Possible increased systemic exposure of DM11

Avoid concomitant use1

Select alternative antifungal with no or minimal CYP3A4 inhibition potential

If concomitant use cannot be avoided, closely monitor patients for adverse effects1

If CYP3A4 inhibitor is discontinued, delay initiation of ado-trastuzumab emtansine (until after approximately 3 half-lives of CYP3A4 inhibitor)1

Antiretrovirals, HIV protease inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir, saquinavir)

Possible increased systemic exposure of DM11

Avoid concomitant use1

Select alternative antiretroviral with no or minimal CYP3A4 inhibition potential

If concomitant use cannot be avoided, closely monitor patients for adverse effects1

If CYP3A4 inhibitor is discontinued, delay initiation of ado-trastuzumab emtansine (until after approximately 3 half-lives of CYP3A4 inhibitor)1

Macrolides (clarithromycin, telithromycin)

Possible increased systemic exposure of DM11

Avoid concomitant use1

Select alternative anti-infective with no or minimal CYP3A4 inhibition potential

If concomitant use cannot be avoided, closely monitor patients for adverse effects1

If CYP3A4 inhibitor is discontinued, delay initiation of ado-trastuzumab emtansine (until after approximately 3 half-lives of CYP3A4 inhibitor)1

Nefazodone

Possible increased systemic exposure of DM11

Avoid concomitant use1

Select alternative antifungal with no or minimal CYP3A4 inhibition potential

If concomitant use cannot be avoided, closely monitor patients for adverse effects1

If nefazodone is discontinued, delay initiation of ado-trastuzumab emtansine (until after approximately 3 half-lives of nefazodone)1

What do I need to tell my doctor BEFORE I take Ado-Trastuzumab Emtansine?

  • If you have an allergy to ado-trastuzumab emtansine or any other part of ado-trastuzumab emtansine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are breast-feeding. Do not breast-feed while you take this medicine or within 7 months after you stop taking it.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take ado-trastuzumab emtansine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Ado-trastuzumab Emtansine Overview

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. Ado-trastuzumab emtansine belongs to a group of drugs called antibody-drug conjugates. It works by killing cancer cells.

Ado-trastuzumab emtansine injection comes as a powder to be mixed with liquid and injected slowly into a vein by a healthcare professional.

Common side effects include constipation, nausea, headache, and fatigue. Do not drive or operate heavy machinery until you know how this medication will affect you.

Ado-trastuzumab Emtansine Genetic Information

Breast cancer is a cancer that forms in the cells of the breasts. Some women have (HER2+) breast cancer. (HER2+) stands for Human Epidermal growth factor receptor 2 positive. (HER2) is a special protein found on breast cancer cells that controls cancer growth and spread.

Ado-trastuzumab emtansine is approved for treatment of HER2 positive breast cancer, because it is specifically designed to target the HER2 protein. By binding to the HER2 protein, ado-trastuzumab emtansine prevents the growth of cancer cells.

HER2 testing is done to see whether treatment with ado-trastuzumab emtansine will likely be effective in treating breast cancer. If testing is not done, treatment with this medication may not be an effective treatment.

 

Side Effects of Ado-trastuzumab Emtansine

Common side effects include the following:

  • constipation
  • diarrhea
  • upset stomach
  • sores in the mouth and throat
  • dry mouth
  • changes in ability to taste
  • joint or muscle pain
  • headache
  • dry, red, or teary eyes
  • blurry vision
  • trouble falling asleep or staying asleep

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
 

Ado-trastuzumab Emtansine Precautions

Serious side effects have been reported with ado-trastuzumab emtansine including the following:

  • Ado-trastuzumab emtansine injection may cause serious infusion-related reactions, which may occur during the infusion of the medication. If you experience any of the following symptoms, tell your doctor immediately: flushing; fever; chills; dizziness; lightheadedness; fainting; shortness of breath; difficulty breathing; or fast, irregular, or pounding heartbeat.
  • Ado-trastuzumab emtansine may cause serious or life-threatening liver problems. Tell your doctor if you have or have ever had liver disease, including hepatitis. Your doctor will order laboratory tests regularly before and during your treatment to see if ado-trastuzumab emtansine is affecting your liver. Your doctor may tell you that you should not receive this medication if the tests show that you have liver problems. Tell your doctor and pharmacist about all the medications you are taking so they can check whether any of your medications may increase the risk that you will develop liver damage during your treatment with ado-trastuzumab emtansine. Call your doctor immediately if you experience any of the following symptoms: nausea, vomiting, extreme tiredness, lack of energy, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, dark-colored urine, or flu-like symptoms.
  • Ado-trastuzumab emtansine also may cause serious or life-threatening heart problems. Tell your doctor if you have or have ever had heart disease, a heart attack, chest pain, or irregular heartbeats. Your doctor will order tests before and during your treatment to see if your heart is working well enough for you to safely receive ado-trastuzumab emtansine. Your doctor may tell you that you should not receive this medication if the tests show your heart's ability to pump blood has decreased. If you experience any of the following symptoms, call your doctor immediately: cough; shortness of breath; swelling of the arms, hands, feet, ankles or lower legs; weight gain (more than 5 pounds [about 2.3 kilograms] in 24 hours); dizziness; loss of consciousness; or fast, irregular, or pounding heartbeat.
  • Tell your doctor if you are pregnant or plan to become pregnant. Ado-trastuzumab emtansine may harm your unborn baby. You should use birth control to prevent pregnancy during your treatment and for 6 months after your treatment. Talk to your doctor about birth control methods that will work for you. If you become pregnant during your treatment with ado-trastuzumab emtansine, call your doctor immediately.

Do not drive or operate heavy machinery until you know how this medication will affect you.

Ado-trastuzumab Emtansine Food Interactions

Grapefruit and grapefruit juice may interact with this medication and can lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Ado-trastuzumab Emtansine and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if this medication crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using this medication.
 

Ado-trastuzumab Emtansine Usage

Ado-trastuzumab emtansine injection comes as a powder to be mixed with liquid and injected slowly into a vein by a healthcare professional. It is usually injected once every 3 weeks. The length of your treatment depends on how well your body responds to the medication and the side effects that you experience.

 

Ado-trastuzumab Emtansine Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight
  • your height
  • your age
  • your gender

The recommended dose is 3.6 mg/kg given every 3 weeks (21-day cycle).

Other Requirements

Keep all appointments with your doctor and the laboratory.

Index Terms

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

Brand Names U.S.

  • Kadcyla

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%

Dosing Adult

Note: Do not substitute ado-trastuzumab emtansine (US) or trastuzumab emtansine (Canada) for or with conventional trastuzumab; products are different and are NOT interchangeable.

Breast cancer, metastatic, HER2+: IV: 3.6 mg/kg every 3 weeks until disease progression or unacceptable toxicity; 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.

In Summary

Commonly reported side effects of ado-trastuzumab emtansine include: increased serum bilirubin, increased serum transaminases, cough, decreased platelet count, dyspnea, fatigue, fever, peripheral neuropathy, and thrombocytopenia. Other side effects include: chills. See below for a comprehensive list of adverse effects.

Other Comments

Administration advice:
-Closely monitor the infusion site for possible subcutaneous infiltration during drug administration.
-Administer the first infusion over 90 minutes. Patients should be observed during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion related reactions.
-Administer subsequent infusions over 30 minutes if prior infusions were well tolerated. Patients should be observed during the infusion and for at least 30 minutes after infusion.
-The infusion rate should be slowed or interrupted if the patient develops an infusion related reaction.
-If a planned dose is delayed or missed, it should be administered as soon as possible; do not wait until the next planned cycle. The schedule of administration should be adjusted to maintain a 3 week interval between doses. The infusion may be administered at the dose and rate the patient tolerated in the most recent infusion.

Storage requirements: Store vials in a refrigerator at 36 to 46 degrees Fahrenheit until time of reconstitution. Do not freeze or shake.

Reconstitution/preparation techniques: Refer to the manufacturer's product information for complete reconstitution instructions.

General:
-In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is ado-trastuzumab emtansine and not trastuzumab.
-Follow procedures for proper handling and disposal of anticancer drugs.

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