Names and pronunciation
(a′doe-tras-tooz′ue-mab) em-tan’seen Kadcyla
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Drug reference
(a′doe-tras-tooz′ue-mab) em-tan’seen Kadcyla
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Func. class.: Antineoplastic-biologic response modifier
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Chem. class.: Signal transduction inhibi- tors (STIs), humanized anti-HER2 antibody
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Do not confuse: ado-trastuzumab/trastuzumab
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ACTION: Humanized anti-HER2 monoclonal antibody that is linked to DM1, a small molecule microtubular inhibitor; once the antibody is bound to the HER2 receptor, the complex is inter- nalized and the DM1 is released to bind with tubulin to lead to apoptosis
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USES: Breast cancer; metastatic with overexpression of HER2, who previously received trastuzumab and a taxane, sepa- rately or in combination
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CONTRAINDICATIONS: Hyper- sensitivity to this product, Chinese ham- ster ovary cell protein
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Black Box Warning: Pregnancy Precautions: Breastfeeding, children, pulmonary disease, acute bronchospasm, anticoagulant, Asian patients, asthma, COPD, extravasation, fever, hepatitis, human antihuman antibody, hypotension, neuropathy, interstitial lung disease/pneu- monitis; extravasation; thrombocytopenia Black Box Warning: Heart failure, hepa- totoxicity Black Box Warning: HF, other cardiac symptoms: dyspnea, coughing; gallop; obtain full cardiac workup including ECG, echo, MUGA; LVEF baseline and q3mo • Symptoms of infection; may be masked by product • CNS reaction: LOC, mental status, diz- ziness, confusion Black Box Warning: Hypersensitivity re- actions, anaphylaxis Black Box Warning: Hepatotoxicity: mon- itor LFTs baseline and prior to each dose; fatal liver damage may occur; reduced dose or discontinuing treatment may be required; monitor for infusion reactions during and for 1.5 hr after infusion; slowing infusion may be needed; monitor LFTs, bili- rubin baseline and prior to each dose • Infusion reactions that may be fatal: fever, chills, nausea, vomiting, pain, headache, dizziness, hypotension; dis- continue product • Pulmonary toxicity: dyspnea, intersti- tial pneumonitis, pulmonary hypertension, ARDS; can occur after infusion reaction; those with lung disease may have more severe toxicity, discontinue in those with pneumonitis, interstitial lung disease • Bleeding: monitor for bleeding; grade 3 or 4 bleeding with fatalities has occurred; check platelets baseline and prior to each dose Black Box Warning: Hepatic disease: may be fatal; monitor LFTs, bilirubin baseline and before each dose Black Box Warning: Pregnancy/breast- feeding: to use effective contraception while taking this product and for 7 mo after discontinuing this drug; to notify prescriber if pregnancy is planned or sus- pected; not to breastfeed; advise patient to enroll in Mother Pregnancy Registry (800-690-6720) • Infusion reactions: to report pain at infusion site
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SIDE EFFECTS CNS: Dizziness, insomnia, neuropathy, chills, fatigue, fever, flushing, headache CV: Hypertension, peripheral edema, left ventricular dysfunction EENT: Blurred vision, conjunctivitis, stomatitis GI: Diarrhea, nausea, vomiting, constipa- tion, dyspepsia, hepatotoxicity HEMA: Anemia, bleeding, thrombocytopenia INTEG: Rash, infusion-related reactions MS: Arthralgia, pain RESP: Cough, dyspnea, pneumonitis, interstitial lung disease SYST: Anaphylaxis OTHER: Elevated LFTs, hand-foot syndrome
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INTERACTIONS • Do not give with other IV products; do not give with 5% dextrose Increase: bleeding risk—warfarin, plate- let inhibitors, anticoagulants Increase: ado-trastuzumab toxicity— CYP3A4 inhibitors (clarithromycin, keto- conazole, ritonavir, saquinavir, atazana- vir); avoid concurrent use
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DOSAGE AND ROUTES • Adult: IV 3.6 mg/kg over 30-90 min q3wk ×14 wk; give first infusion over 90 min; if tolerated, give over 30 min Dosage adjustments for toxicities Hepatotoxicity: • AST/ALT >5 to ≤20 × ULN: withhold, resume at a reduced dose when AST/ ALT is ≤5 × ULN; first dose reduction: re- duce the dose to 3 mg/kg; second dose reduction: reduce the dose to 2.4 mg/ kg; requirement for further dose reduc- tion: discontinue AST/ ALT >20× ULN: discontinue • Total bilirubin >3 to ≤10× ULN: with- hold, resume treatment at a reduced dose when total bilirubin recovers to ≤1.5; first dose reduction: reduce the dose to 3 mg/ kg; second dose reduction: reduce the dose to 2.4 mg/kg; requirement for further dose reduction: discontinue treatment • Total bilirubin >10× ULN: permanently discontinue; permanently discontinue treat- ment in patients with AST/ALT >3× ULN and total bilirubin >2× ULN; permanently dis- continue treatment in patients diagnosed with nodular regenerative hyperplasia (NRH) • Left ventricular ejection fraction (LVEF): LVEF 40%-45% and decrease is <10% from baseline: continue; repeat LVEF assessment within 3 wk; LVEF 40%- 45% and decrease is ≥10% from baseline: withhold; repeat LVEF assessment within 3 wk; if LVEF remains ≥10% from base- line, discontinue; LVEF <40%: withhold; repeat LVEF assessment within 3 wk; if LVEF remains <40%, discontinue; symp- tomatic heart failure (HF): discontinue Thrombocytopenia: • Platelet 25,000/mm3 count to <50,000/mm3: withhold; resume at same dose when platelet count recovers to ≥75,000/mm3 • Platelet count <25,000/mm3: with- hold; resume at a reduced dose when platelet count recovers to ≥75,000/mm3: first reduction: reduce the dose to 3 mg/ kg; second reduction: reduce the dose to 2.4 mg/kg; requirement for further reduc- tion: discontinue Pulmonary toxicity: • Permanently discontinue in interstitial lung disease or pneumonitis Peripheral neuropathy: • Withhold in grade 3 or 4 peripheral neuropathy; resume upon resolution to ≤grade 2
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Available forms: lyophilized powder 100, 160 mg/vial
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Administer: IV route • Visually inspect for particulate matter and discoloration before use • Give as infusion with a 0.2- or 0.22- micron in-line filter; do not administer as an IV push or bolus • Use cytotoxic handling procedures; do not mix with, or administer as an infu- sion with, other IV products Reconstitution: • Slowly inject 5 mL of sterile water for injection into each 100-mg vial or 8 mL of sterile water for injection into each 160-mg vial to yield a single-use solution of 20 mg/mL • Direct the stream of sterile water to- ward the wall of the vial • Gently swirl the vial; do not shake • After reconstitution, withdraw amount and dilute immediately in 250 mL of 0.9% sodium chloride; gently invert the bag to mix • The reconstituted single-use product does not contain a preservative; use the diluted solution immediately or store at 36°F-46°F (2°C-8°C) for up to 24 hr after reconstitution; discard any unused drug after 24 hr; do not freeze IV infusion • Closely monitor for possible subcutane- ous infiltration during administration • First infusion: give over 90 min; the infusion rate should be slowed or inter- rupted if the patient develops an infusion- related reaction; observe for at least 90 min following the initial dose for fever, chills, or other infusion-related reac- tions; permanently discontinue for life- threatening infusion-related reactions • Subsequent infusions: administer over 30 min if prior infusions were well tolerated; the infusion rate should be slowed or interrupted if the patient devel- ops an infusion-related reaction; observe for at least 30 min after the infusion; perma- nently discontinue for life-threatening infusion-related reactions
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Assess: • Pregnancy test, CBC, differential, LFTs
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Evaluate: • Therapeutic response: decrease in size, spread of breast cancer
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • Reason for product, expected result • To take acetaminophen for fever • To avoid hazardous tasks because confusion, dizziness may occur • To report signs of infection: sore throat, fever, diarrhea, vomiting; bleeding; de- creased heart function/SOB with exertion • To report weight gain; swelling of the ankles, feet; fatigue; cough; bleeding
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PHARMACOKINETICS A 93% protein binding, metabolized in the liver by CYP3A4, half-life 4 days
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• Adult: IV 3.6 mg/kg over 30-90 min q3wk ×14 wk; give first infusion over 90 min; if tolerated, give over 30 min Dosage adjustments for toxicities Hepatotoxicity:
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• AST/ALT >5 to ≤20 × ULN: withhold, resume at a reduced dose when AST/ ALT is ≤5 × ULN; first dose reduction: re- duce the dose to 3 mg/kg; second dose reduction: reduce the dose to 2.4 mg/ kg; requirement for further dose reduc- tion: discontinue AST/ ALT >20× ULN: discontinue
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• Total bilirubin >3 to ≤10× ULN: with- hold, resume treatment at a reduced dose when total bilirubin recovers to ≤1.5; first dose reduction: reduce the dose to 3 mg/ kg; second dose reduction: reduce the dose to 2.4 mg/kg; requirement for further dose reduction: discontinue treatment
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• Total bilirubin >10× ULN: permanently discontinue; permanently discontinue treat- ment in patients with AST/ALT >3× ULN and total bilirubin >2× ULN; permanently dis- continue treatment in patients diagnosed with nodular regenerative hyperplasia (NRH)
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• Left ventricular ejection fraction (LVEF): LVEF 40%-45% and decrease is <10% from baseline: continue; repeat LVEF assessment within 3 wk; LVEF 40%- 45% and decrease is ≥10% from baseline: withhold; repeat LVEF assessment within 3 wk; if LVEF remains ≥10% from base- line, discontinue; LVEF <40%: withhold; repeat LVEF assessment within 3 wk; if LVEF remains <40%, discontinue; symp- tomatic heart failure (HF): discontinue Thrombocytopenia:
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• Platelet 25,000/mm3 count to <50,000/mm3: withhold; resume at same dose when platelet count recovers to ≥75,000/mm3
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• Platelet count <25,000/mm3: with- hold; resume at a reduced dose when platelet count recovers to ≥75,000/mm3: first reduction: reduce the dose to 3 mg/ kg; second reduction: reduce the dose to 2.4 mg/kg; requirement for further reduc- tion: discontinue Pulmonary toxicity:
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• Permanently discontinue in interstitial lung disease or pneumonitis Peripheral neuropathy:
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• Withhold in grade 3 or 4 peripheral neuropathy; resume upon resolution to ≤grade 2
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