Ado-Trastuzumab Emtansine

Ado-Trastuzumab Emtansine is a prescription medication used to treat the symptoms of breast cancer.    

• Ado-Trastuzumab Emtansine is available under the following different brand names: Kadcyla

Adult dosage

Injection of lyophilized powder for reconstitution

• 100mg/vial
• 160mg/vial
• 20mg/mL following reconstitution

Breast Cancer

Adult dosage

Early breast cancer

• 3.6 mg/kg Intravenous every 3 weeks
• Do not administer at doses above 3.6 mg/kg
• Continue treatment for a total of 14 cycles unless there is disease recurrence or unacceptable toxicity

Metastatic breast cancer

• 3.6 mg/kg Intravenous every 3 weeks
• Do not administer at doses above 3.6 mg/kg
• Continue until disease recurrence or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Ado-Trastuzumab Emtansine include:

• diarrhea,
• redness or irritation at the injection site,
• dizziness,
• muscle or joint pain,
• back pain,
• stomach pain,
• trouble sleeping,
• vomiting,
• mouth sores,
• dry mouth,
• changes in taste, and
• loss of appetite,

Serious side effects of Ado-Trastuzumab Emtansine include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• bone pain,
• increased coughing,
• swelling of the hands, ankles, or feet,
• unusual tiredness,
• severe headache,
• tingling and numbness (hands, feet, or legs),
• mood changes,
• fast or pounding heartbeat,
• muscle cramps,
• easy bruising or bleeding,
• weakness on one side of the body,
• slurred speech,
• vision changes,
• confusion,
• severe stomach or abdominal pain,
• vomit that is bloody or looks like coffee grounds,
• black or tarry stools,
• fever,
• chills,
• persistent sore throat,
• cough,
• flushing,
• wheezing,
• shortness of breath,
• nausea,
• headache,
• dizziness,
• fainting,
• rash,
• weakness, and
• skin rash

Rare side effects of Ado-Trastuzumab Emtansine include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ado-Trastuzumab Emtansine has severe interactions with no other drugs.
• Ado-Trastuzumab Emtansine has serious interactions with at least 40 other drugs.
• Ado-Trastuzumab Emtansine has moderate interactions with at least 26 other drugs.
• Ado-Trastuzumab Emtansine has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ado-Trastuzumab Emtansine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ado-Trastuzumab Emtansine?”

Cautions

• Hepatotoxicity, predominantly in the form of asymptomatic, transient increases in the concentrations of serum transaminases, reported (see Black Box Warnings and Dosage Modifications)
• Cases of nodular regenerative hyperplasia of the liver were reported; upon diagnosis of nodular regenerative hyperplasia of the liver, treatment must be permanently discontinued
• CHF and more than 10% reduction in LVEF in patients with HER2-positive metastatic breast cancer with a baseline LVEF of 40-49% that received treatment reported (see Black Box Warnings and Dosage Modifications)
• Discontinue treatment permanently if the patient diagnosed with nodular regenerative hyperplasia
• Known to cause fetal harm and death (see Black Box Warnings)
• Pulmonary toxicity may occur; cases of interstitial lung disease, including pneumonitis reported, permanently discontinue the drug (see Dosage Modifications)
• For patients with radiation pneumonitis in the adjuvant setting, therapy should be permanently discontinued for grades greater than or equal to 3 or for grade 2 not responding to standard treatment
• Patients with dyspnea at rest due to complications of advanced malignancy, co-morbidities, and receiving concurrent pulmonary radiation therapy may be at increased risk of pulmonary toxicity
• Infusion-related reactions (IRRs) and/or hypersensitivity may occur; temporarily interrupt infusion for severe IRRs and permanently discontinue if life-threatening IRR occurs
• Thrombocytopenia or decreased platelet counts were reported (see Dosage Modifications)
• Hemorrhagic events (including CNS, respiratory, and GI hemorrhage) have been reported; although, in some cases, patients were also receiving anticoagulation therapy, antiplatelet therapy, or had thrombocytopenia, in others there were no known additional risk factors; use caution with these agents and consider additional monitoring when concomitant use is medically necessary
• Peripheral neuropathy may occur (see Dosage Modifications)
• Extravasation observed during clinical trials; carefully monitor infusion site during infusion and inform patient to report any tenderness/redness
• Cases of possible tumor lysis syndrome (TLS) reported in patients treated; patients with significant tumor burden (e.g., bulky metastases) may be at a higher risk; patients could present with hyperuricemia, hyperphosphatemia, and acute renal failure which may represent possible TLS; providers should consider additional monitoring and/or treatment as clinically indicated
• Drug interactions overview
  • DM1, the cytotoxic component of ado-trastuzumab emtansine, is a CYP3A4 substrate
  • Avoid concomitant use of strong CYP3A4 inhibitors owing to the potential for an increase in DM1 exposure and toxicity; consider an alternative with no or minimal potential to inhibit CYP3A4
  • If concomitant use of strong CYP3A4 inhibitors is unavoidable, consider delaying ado-trastuzumab emtansine until strong CYP3A4 inhibitors have cleared from the circulation (~3 elimination half-lives of the inhibitors) when possible
  • If a strong CYP3A4 inhibitor is Coad ministered and ado-trastuzumab emtansine cannot be delayed, closely monitor the patient for adverse reactions

Pregnancy & Lactation

Therapy can cause fetal harm when administered to a pregnant woman

• No data is available on use in pregnant women; cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death were observed in the postmarketing setting in patients treated with trastuzumab, the antibody component
• Based on the mechanism of action, the DM1 component can also cause embryofetal harm when administered to a pregnant woman
• Advise patient of potential risks to a fetus; there are clinical considerations if the drug is used in a pregnant woman, or if a patient becomes pregnant within 7 months following the last dose
• Pregnancy pharmacovigilance program
  • If administered during pregnancy, or if a patient becomes pregnant while receiving therapy or within 7 months following the last dose, immediately report ado-trastuzumab emtansine exposure to Genentech at 1-888-835-2555
• Reproductive potential
  • Verify pregnancy status of females of reproductive potential before initiation of therapy
• Contraception
  • Females: Drug can cause embryofetal harm when administered during pregnancy; advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose
  • Males: Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months following the last dose
• Infertility
  • Based on results from animal toxicity studies, therapy may impair fertility in females and males of reproductive potential; not known if the effects are reversible
• Lactation
  • There is no information regarding the presence of ado-trastuzumab emtansine in human milk, effects on the breastfed infant, or milk production; DM1, the cytotoxic component of the drug, may cause serious adverse reactions in breastfed infants based on its mechanism of action; advise women not to breastfeed during treatment and for 7 months following the last dose of the drug