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KADCYLA (Ado-Trastuzumab Emtansine) and Not Trastuzumab

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KADCYLA (Ado-Trastuzumab Emtansine) and Not Trastuzumab HIGHLIGHTS OF PRESCRIBING INFORMATION interruption, dose reduction, or treatment discontinuation of These highlights do not include all the information needed to use KADCYLA. (2.3) KADCYLA safely and effectively. See full prescribing information for KADCYLA. DOSAGE FORMS AND STRENGTHS Lyophilized powder in single-dose vials containing 100 mg per vial or 160 mg KADCYLA® (ado-trastuzumab emtansine) for injection, for intravenous per vial. (3) use Initial U.S. Approval: 2013 CONTRAINDICATIONS None. (4) WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning WARNINGS AND PRECAUTIONS Hepatotoxicity, liver failure and death have occurred in Pulmonary Toxicity: Permanently discontinue KADCYLA in patients KADCYLA-treated patients. Monitor hepatic function diagnosed with interstitial lung disease or pneumonitis. For patients with prior to initiation and prior to each dose. Institute dose radiation pneumonitis in the adjuvant setting, permanently discontinue modifications or permanently discontinue as appropriate. KADCYLA for Grade 3 or for Grade 2 not responding to standard (2.3, 5.1) treatment. (2.2, 5.4) KADCYLA may lead to reductions in left ventricular Infusion-Related Reactions, Hypersensitivity Reactions: Monitor for ejection fraction (LVEF). Assess LVEF prior to signs and symptoms during and after infusion. If significant infusion- initiation. Monitor and withhold dosing or discontinue as related reactions or hypersensitivity reactions occur, slow or interrupt appropriate. (2.3, 5.2) the infusion and administer appropriate medical therapies. Permanently Embryo-Fetal Toxicity: Exposure to KADCYLA during discontinue KADCYLA for life threatening infusion-related reaction. pregnancy can result in embryo-fetal harm. Advise (2.1, 2.2, 5.5) patients of these risks and the need for effective Hemorrhage: Fatal cases of hemorrhage occurred in clinical trials among contraception. (5.3, 8.1, 8.3) 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 RECENT MAJOR CHANGES additional monitoring when concomitant use is medically necessary. Indications and Usage (1.2) 05/2019 (5.6) Dosage and Administration (2.1, 2.2, 2.3) 05/2019 Thrombocytopenia: Monitor platelet counts prior to each KADCYLA Warnings and Precautions (5.1, 5.2, 5.4, 5.8) 05/2019 dose. Institute dose modifications as appropriate. (2.2, 5.7) Neurotoxicity: Monitor for signs or symptoms. Withhold dosing INDICATIONS AND USAGE temporarily for patients experiencing Grade 3 or 4 peripheral KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate neuropathy. (2.2, 5.8, 13.2) indicated, as a single agent, for: the treatment of patients with HER2-positive, metastatic breast cancer ADVERSE REACTIONS who previously received trastuzumab and a taxane, separately or in Metastatic Breast Cancer combination. Patients should have either: The most common adverse reactions ( 25%) with KADCYLA were received prior therapy for metastatic disease, or fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, developed disease recurrence during or within six months of headache, increased transaminases, constipation and epistaxis. (6.1) completing adjuvant therapy. (1.1) Early Breast Cancer the adjuvant treatment of patients with HER2-positive early breast cancer The most common adverse reactions ( 25%) with KADCYLA were who have residual invasive disease after neoadjuvant taxane and fatigue, nausea, increased transaminases, musculoskeletal pain, trastuzumab-based treatment. (1.2) hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia. Select patients for therapy based on an FDA-approved companion diagnostic for KADCYLA [see Dosage and Administration (2.1)] To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DOSAGE AND ADMINISTRATION Do not substitute KADCYLA for or with trastuzumab. HER2 Testing: Perform using FDA-approved tests by laboratories with USE IN SPECIFIC POPULATIONS demonstrated proficiency. (2.1) Lactation: Advise not to breastfeed. (8.2) For intravenous infusion only. Do not administer as an intravenous push Females and Males of Reproductive Potential: Verify pregnancy status or bolus. Do not use Dextrose (5%) solution. (2.4) of females prior to initiation of KADCYLA. (8.3) The recommended dose of KADCYLA is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease See 17 for PATIENT COUNSELING INFORMATION. progression or unacceptable toxicity, or a total of 14 cycles for patients with EBC. Do not administer KADCYLA at doses greater than 3.6 Revised: 05/2019 mg/kg. (2.2) Management of adverse reactions (infusion-related reactions, hepatotoxicity, left ventricular cardiac dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy) may require temporary 1 of 31 Reference ID: 4428535 FULL PRESCRIBING INFORMATION: CONTENTS* 8 Use in Specific Populations 1 INDICATIONS AND USAGE 8.1 Pregnancy 1.1 Metastatic Breast Cancer (MBC) 8.2 Lactation 1.2 Early Breast Cancer (EBC) 8.3 Females and Males of Reproductive Potential 2 DOSAGE AND ADMINISTRATION 8.4 Pediatric Use 2.1 Patient Selection 8.5 Geriatric Use 2.2 Recommended Doses and Schedules 8.6 Renal Impairment 2.3 Dose Modifications 8.7 Hepatic Impairment 2.4 Preparation for Administration 10 Overdosage 3 Dosage Forms and Strengths 11 Description 4 Contraindications 12.1 Mechanism of Action 5 Warnings and Precautions 12.2 Pharmacodynamics 5.1 Hepatotoxicity 12.3 Pharmacokinetics 5.2 Left Ventricular Dysfunction 13 Nonclinical Toxicology 5.3 Embryo-Fetal Toxicity 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.4 Pulmonary Toxicity 13.2 Animal Toxicology and/or Pharmacology 5.5 Infusion-Related Reactions, Hypersensitivity Reactions 14 Clinical Studies 5.6 Hemorrhage 14.1 Metastatic Breast Cancer 5.7 Thrombocytopenia 14.2 Early Breast Cancer 5.8 Neurotoxicity 15 REFERENCES 5.9 Extravasation 16 How Supplied/Storage and Handling 6 Adverse Reactions 16.1 How Supplied/Storage 6.1 Clinical Trials Experience 16.2 Special Handling 6.2 Immunogenicity 17 Patient Counseling Information 7 Drug Interactions * Sections or subsections omitted from the Full Prescribing Information are not listed. 2 of 31 Reference ID: 4428535 FULL PRESCRIBING INFORMATION WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY DoHepatotoxicity: Not Substitute Serious KADCYLA hepat forotoxicity or with has trastuzumab. been reported, (2.1) inc luding liver failure Hepatotoxicity:and death in patients Serious treated hepat withotoxicity KADCYLA. has been Monitor reported, serum including transaminases liver failure and deathbilirubin in patients prior to treatedinitiatio withn of KADCYLAKADCYLA. treatment Monitor serum and prio transr toaminases each KADCYLA dose. Reduce dose or discontinue KADCYLA as appropriate in cases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLAof increased dose.serum Reduce transamina dose sesor disor continuetotal bilirubin. KADCYLA (2.3, 5.1) as appropriate in cases ofCardiac increased Toxicity: serum KADCYLA transamina sesadmi ornistration total bilirubin. may lea (2.2,d to 5.1) reduction s in left Cardiacventricular Toxicity: ejection KADCYLA fraction (LVEF). administration Evaluate may left ventriculalead to reductionr functions in inleft all ventricularpatients prior ejection to and fraction during trea(LVEF).tment Evaluate with KADCYLA. left ventricula Withholdr function treatment in all for patientsclinically prior significant to and decrease during trea in lefttment ventricular with KADCYLA. function. (Withhold2.3, 5.2) treatment for clinicallyEmbryo-Fetal significant Toxicity: decrease Exposu in releft to ventricular KADCYLA function. during pregnancy(2.2, 5.2) can result in Embryo-Fetalembryo-fetal harm. Toxicity: Advise Exposu patientsre to of KADCYLA these risks duringand the pregnancy need for effective can result in embryo-fetalcontraception. harm. (5.3, 8.1, Advise 8.3) patients of these risks and the need for effective contraception (5.3, 8.1, 8.3). 1 INDICATIONS AND USAGE 1.1 Metastatic Breast Cancer (MBC) KADCYLA®, as a single agent, is indicated for the 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. Select patients for therapy based on an FDA-approved companion diagnostic for KADCYLA [see Dosage and Administration (2.1)]. 1.2 Early Breast Cancer (EBC) KADCYLA, as a single agent, 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. Select patients for therapy based on an FDA-approved companion diagnostic for KADCYLA [see Dosage and Administration (2.1)] 2 DOSAGE AND ADMINISTRATION 2.1 Patient Selection Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1), Clinical Studies (14)]. Assessment of HER2 protein overexpression and/or HER2 gene amplification should be performed using FDA-approved tests specific for
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