HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.
A HER2-targeted antibody and microtubule inhibitor conjugate. Trastuzumab, the antibody, attaches to receptors and is taken into the cell, where the microtubule inhibitor, DM1, causes cell cycle arrest and death.
Decreased spread of metastatic breast cancer, with improved progression-free survival.
Absorption: IV administration results in complete bioavailability.
Metabolism and Excretion: DM1 is metabolized by CYP3A4/5.
Half-life: 4 days.
TIME/ACTION PROFILE (comparative improvement in progression-free survival)
|IV||4–6 mos||10–12 mos||2 yr|
- Interstitial lung disease or pneumonitis;
- Concurrent use of strong CYP3A4 inhibitors;
- OB: May cause fetal harm;
- Lactation:Breast feeding should be avoided.
Use Cautiously in:
- Underlying cardiovascular or pulmonary disease, including dyspnea at rest;
- Rep: Women of reproductive potential and men with female partners of reproductive potential should use effective contraception;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: fatigue, headache, dizziness, insomnia, weakness
Resp: PULMONARY TOXICITY, cough
EENT: blurred vision, conjunctivitis, dry eyes, ↑ lacrimation
CV: LEFT VENTRICULAR DYSFUNCTION, hypertension, peripheral edema
GI: HEPATOTOXICITY, constipation, ↑ liver enzymes, nausea, altered taste, diarrhea, dry mouth, dyspepsia, stomatitis, vomiting
Derm: pruritus, rash
F and E: hypokalemia
GU: ↓ fertility
Hemat: HEMORRHAGE, THROMBOCYTOPENIA, anemia, neutropenia
MS: musculoskeletal pain, arthralgia, myalgia
Neuro: peripheral neuropathy
Misc: HYPERSENSITIVITY REACTIONS, chills, infusion-related reactions, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Blood levels and risk of toxicity may be ↑ by concurrent use of strong inhibitors of CYP3A4 including atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and voriconazole, and should be avoided, waiting 3 half-lives of inhibitor to start treatment.
- Concurrent use of anticoagulants, or antiplatelet agents, especially during the first cycle, may ↑ risk of bleeding.
IV: (Adults) 3.6 mg/kg every 3 wk continued until disease progresses or unacceptable toxicity occurs.
Lyophilized powder for intravenous injection (requires reconstitution): 100 mg/vial, 160 mg/vial
- Evaluate left ventricular function in all patients prior to and every 3 mo during therapy. If symptomatic HF: discontinue ado-trastuzumab. If left ventricular ejection fraction (LVEF) <40%: Hold dose. Repeat LVSF assessment within 3 wks. If LVEF <40% is confirmed, discontinue therapy. If LVEF 40% to ≤45% and decrease is ≥10% points from baseline: Hold dose. Repeat LVEF within 3 wks. If LVEF has not recovered to within 10% points from baseline, discontinue therapy. If LVEF 40% to ≤45% and decrease is <10% points from baseline: Continue therapy with ado-trastuzumab. Repeat LVEF within 3 wks. If LVEF >45%: Continue therapy.
- Monitor infusion site closely for infiltration and extravasation closely. Within 24 hrs erythema, tenderness, skin irritation, pain, or swelling at infusion site is seen if extravasation occurs.
- Assess for signs and symptoms of infusion reactions (fever, chills, flushing, dyspnea, hypotension, wheezing, bronchospasm, tachycardia). Interrupt therapy if symptoms are severe. Observe closely during first infusion. Permanently discontinue for life-threatening reactions.
- Monitor neurologic status before and during treatment. Assess for paresthesia (numbness, tingling, pain, burning sensation), loss of deep tendon reflexes (Achilles reflex is usually first involved), weakness (wrist drop or footdrop, gait disturbances), cranial nerve palsies (jaw pain, hoarseness, ptosis, visual changes), arthralgia, myalgia, muscle spasm, autonomic dysfunction (ileus, difficulty voiding, orthostatic hypotension, impaired sweating), and CNS dysfunction (decreased level of consciousness, agitation, hallucinations). Temporarily discontinue therapy in patients with Grade 3 or 4 peripheral neuropathy (severe symptoms; limiting self-care activities of daily living (ADL) until resolution to ≤ Grade 2 (moderate symptoms; limiting instrumental ADL) neuropathy.
- Monitor for signs and symptoms of pulmonary toxicity (dyspnea, cough, fatigue, pulmonary infiltrates). Permanently discontinue therapy if interstitial lung disease or pneumonitis develops.
- Monitor for hemorrhage (central nervous system, respiratory, gastrointestinal hemorrhage) during therapy, especially in patients receiving anticoagulants, antiplatelet therapy, or who have thrombocytopenia.
Lab Test Considerations:
HER2 protein overexpression is used to determine whether treatment with ado-trastuzumab is indicated. HER2 protein overexpression should be determined by labs with proficiency in specific technology used.
- Monitor serum transaminases and bilirubin prior to starting therapy and before each dose. If AST/ALT is Grade 2 (>2.5 to ≤5 × upper limit of normal): Treat at same dose. If AST/ALT is Grade 3 (>5 to ≤20 × upper limit of normal): Do not administer ado-trastuzumab until AST/ALT recovers to Grade ≤2, and then reduce 1 dose level. If AST/ALT is Grade 4 (>20 × upper limit of normal): Permanently discontinue ado-trastuzumab. If serum bilirubin is Grade 2 (>1.5 to ≤3 × upper limit of normal) : Hold dose until bilirubin recovers to Grade ≤1, then treat at same dose level. If bilirubin is Grade 3 (>3 to ≤10 × upper limit of normal): Hold dose until bilirubin recovers to Grade ≤1, then reduce 1 dose level. If bilirubin is Grade 4 (>10 × upper limit of normal): Permanently discontinue ado-trastuzumab. Permanently discontinue ado-trastuzumab in patients with AST/ALT >3 × upper limit of normal and concomitant total bilirubin >2 × upper limit of normal.
- Monitor platelet count prior to starting therapy and before each dose. Nadir of thrombocytopenia occurs by Day 8 and generally improves to Grade 0 or 1 by next scheduled dose. If thrombocytopenia is Grade 3 (PLT 25,000/mm3 to <50,000/mm3 : Hold dose until platelet count recovers to ≤Grade 1 (≥75,000/mm3 ), then treat at same dose level. If thrombocytopenia is Grade 4 (PLT <25,000/mm3 ): Hold dose until platelet count recovers to ≤Grade 1, then reduce 1 dose level.
- May cause ↓ hemoglobin, neutrophils, and serum potassium.
- Deficient knowledge, related to medication regimen (Patient/Family/Teaching)
- High Alert: Do not confuse ado-trastuzumab (Kadcyla) with trastuzumab (Herceptin). Double check names. Trade name of administered product should be clearly recorded in patient file to improve traceability.
- High Alert:Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, dose calculations and infusion pump settings.
- Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
- Y-Site Incompatibility
- Do not mix or administer with other medications.
- Intermittent Infusion: Reconstitute by slowly inject 5 or 8 mL of Sterile Water for Injection into 100 or 160 mg vial of ado-trastuzumab respectively, for a solution of 20 mg/mL. Swirl gently until dissolved; do not shake. Solution is clear, colorless to pale brown, and slightly opalescent; do not administer solutions that are discolored or contain particulate matter. Use reconstituted vials immediately or store in refrigerator up to 4 hr; then discard. Do not freeze. Calculate amount of solution needed. Diluent: Withdraw from vial and add to infusion bag containing 250 mL of 0.9% NaCl; do not use dextrose solutions. Gently invert bag to mix without foaming. Use diluted solution immediately; may be stored in refrigerator up to 24 hrs prior to use, then discard; do not freeze or shake. Administer every 3 wks (21–day cycle); if cycle is delayed, administer as soon as possible. Do not wait until next planned cycle; maintain 3-wk interval between doses.
- Rate: Infuse through a 0.2 or 0.22 micron in-line non-protein adsorptive polyethersulfone (PES) filter. Do not administer as IV push or bolus. First infusion: Infuse over 90 min; observe for infusion related reaction. Subsequent infusions: Infuse over 30 min if prior infusions were well tolerated. Observe patient during infusion and for at least 90 min after infusion.
- Management of increased serum transaminases, hyperbilirubinemia, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity, or peripheral neuropathy may require temporary interruption, dose reduction, or discontinuation.
- Dose reduction schedule is: Starting dose– 3.6 mg/kg; First dose reduction– 3 mg/kg; Second dose reduction– 2.4 mg/kg; Requirement for further dose reduction– discontinue therapy.
- Explain purpose of medication to patient.
- Inform patient of potential liver injury and HF. Advise patient to notify health care professional immediately if signs and symptoms of liver injury (nausea, vomiting, abdominal pain, jaundice, dark urine, pruritus, anorexia) or HF (new onset or worsening shortness of breath, cough, swelling of ankles/legs, palpitations, weight gain of >5 lbs in 24 hrs, dizziness, loss of consciousness) occur.
- Advise patient to notify health care professional if signs of peripheral neuropathy (burning, numbness, pain in hands and feet/legs) occur.
- Rep: Ado-trastuzumab can cause fetal harm. Advise male and female patients to use a highly effective method (IUD, hormonal contraceptive, tubal ligation, partner's vasectomy) of contraception during and for at least 4 mo after last dose. Instruct patient to notify health care professional promptly if pregnancy is suspected and to avoid breast feeding for at least 7 mo after last dose. Encourage women who have been exposed to ado-trastuzumab either directly or through seminal fluid, to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 and to immediately report exposure to Genentech Adverse Event Line at 1-888-835-2555.
Decreased spread of metastatic breast cancer.
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