Ado-trastuzumab emtansine

What is Ado-trastuzumab emtansine?

• Ado-trastuzumab emtansine (Kadcyla) is a HER2-targeted antibody and microtubule inhibitor conjugate used for the treatment of patients with HER2-positive, metastatic breast cancer.

What are the uses of this medicine?

This medicine is used for: Metastatic Breast Cancer (MBC)

• Kadcyla treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.

Patients should have either:

• Received prior therapy for metastatic disease, or
• Developed disease recurrence during or within six months of completing adjuvant therapy.

Early Breast Cancer (EBC):

• This medicine is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab -based treatment.

How does this medicine work?

• Ado-trastuzumab emtansine is a HER2-targeted antibody-drug conjugate.
• The antibody is the humanized anti-HER2 IgG1, trastuzumab.
• The small molecule cytotoxin, DM1, is a microtubule inhibitor.
• Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites.
• Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death.
• In addition, in vitro studies have shown that similar to trastuzumab, ado-trastuzumab emtansine inhibits HER2 receptor signaling, mediates antibody-dependent cell-mediated cytotoxicity and inhibits shedding of the HER2 extracellular domain in human breast cancer cells that overexpress HER2.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• No formal drug-drug interaction studies with Kadcyla have been conducted.

Is this medicine FDA approved?

FDA approved this drug in the year of 2013.

How should this medicine be used?

• Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens.
• Do not substitute Kadcyla for or with trastuzumab.

Recommended Dosage:

• The recommended dose of Kadcyla is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity, or a total of 14 cycles for patients with EBC.
• Management of adverse reactions (infusion-related reactions, hepatotoxicity, left ventricular cardiac dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy) may require temporary interruption, dose reduction, or treatment discontinuation of Kadcyla.

Metastatic Breast Cancer (MBC) Patients with MBC should receive treatment until disease progression or unmanageable toxicity.

Early Breast Cancer (EBC) Patients with EBC should receive treatment for a total of 14 cycles unless there is disease recurrence or unmanageable toxicity.

Administration

• Administer Kadcyla as an intravenous infusion only with a 0.2 or 0.22 micron in-line polyethersulfone (PES) filter. Do not administer as an intravenous push or bolus.
• Do not mix Kadcyla, or administer as an infusion, with other medicinal products.
• First infusion: Administer infusion over 90 minutes. Observe patients during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion-related reactions.
• Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated. Observe patients during the infusion and for at least 30 minutes after infusion.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Lyophilized powder in single-dose vials containing 100 mg per vial or 160 mg per vial.

This medicine is available in fallowing brand namesː

• Kadcyla

What side effects can this medication cause?

The most common side effects of this medicine include: Metastatic Breast Cancer:

• fatigue
• nausea
• musculoskeletal pain
• hemorrhage
• thrombocytopenia
• headache
• increased transaminases
• constipation
• epistaxis

Early Breast Cancer:

• fatigue
• nausea
• increased transaminases
• musculoskeletal pain
• hemorrhage
• thrombocytopenia
• headache
• peripheral neuropathy
• arthralgia

What special precautions should I follow?

• Cases of interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome have been reported in clinical trials with Kadcyla. Permanently discontinue Kadcyla in patients diagnosed with interstitial lung disease or pneumonitis. For patients with radiation pneumonitis in the adjuvant setting, permanently discontinue Kadcyla for Grade ≥ 3 or for Grade 2 not responding to standard treatment.
• Infusion-related reactions, characterized by one or more of the following symptoms − flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, and tachycardia have been reported in clinical trials of Kadcyla. Monitor for signs and symptoms during and after infusion. If significant infusion-related reactions or hypersensitivity reactions occur, slow or interrupt the infusion and administer appropriate medical therapies. Permanently discontinue Kadcyla for life threatening infusion-related reaction.
• Cases of hemorrhagic events, including central nervous system, respiratory, and gastrointestinal hemorrhage, have been reported in clinical trials with Kadcyla. Fatal cases of hemorrhage occurred in clinical trials among patients with no known identified risk factors, as well as among patients with thrombocytopenia and those receiving anti-coagulation and antiplatelet therapy. Use caution with these agents and consider additional monitoring when concomitant use is medically necessary.
• Thrombocytopenia, or decreased platelet count, was reported in clinical trials of Kadcyla. Monitor platelet counts prior to each Kadcyla dose. Institute dose modifications as appropriate.
• Peripheral neuropathy, mainly as Grade 1 and predominantly sensory, was reported in clinical trials of Kadcyla. Monitor for signs or symptoms. Withhold dosing temporarily for patients experiencing Grade 3 or 4 peripheral neuropathy.
• Hepatotoxicity, predominantly in the form of asymptomatic, transient increases in the concentrations of serum transaminases, has been observed in clinical trials with Kadcyla. Monitor serum transaminases and bilirubin prior to initiation of Kadcyla treatment and prior to each Kadcyla dose.
• Patients treated with Kadcyla are at increased risk of developing left ventricular dysfunction. Assess LVEF prior to initiation of Kadcyla and at regular intervals (e.g. every three months) during treatment to ensure the LVEF is within the institution's normal limits. Kadcyla has not been studied in an adequately controlled study in patients with LVEF.
• Kadcyla can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of Kadcyla.

What to do in case of emergency/overdose?

Symptoms of overdosage may include: thrombocytopenia

Management for overdosage:

• There is no known antidote for overdose of Kadcyla.

Can this medicine be used in pregnancy?

• Kadcyla can cause fetal harm when administered to a pregnant woman.
• There are no available data on the use of Kadcyla in pregnant women.

Can this medicine be used in children?

• Safety and effectiveness of Kadcyla have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active Ingredient:

• ADO-TRASTUZUMAB EMTANSINE

Inactive Ingredients:

• SUCROSE
• SUCCINIC ACID
• SODIUM HYDROXIDE
• POLYSORBATE 20
• WATER

Who manufactures and distributes this medicine?

Manufactured by:

• Genentech, Inc.
• A Member of the Roche Group
• 1 DNA Way
• South San Francisco

What should I know about storage and disposal of this medication?

• Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution.
• Do not freeze or shake.
• Follow procedures for proper handling and disposal of anticancer drugs.

• Dailymed label info on Ado-trastuzumab emtansine
• FDA Ado-trastuzumab emtansine

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