• HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.

Contraindicated in:

• 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.

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.

Drug-Drug:

• 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.

• Lyophilized powder for intravenous injection (requires reconstitution): 100 mg/vial; 160 mg/vial;

• IV (Adults): 3.6 mg/kg every 3 wk continued until disease progresses or unacceptable toxicity occurs.

Kadcyla

• 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.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: drug-antibody conjugates

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: DM1 is metabolized by CYP3A4/5.

Half-life: 4 days.

(comparative improvement in progression-free survival)

• 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.

ado-trastuzumab: ado tras-TOO-zoo-mab