ado-trastuzumab, Kadcyla

 Classification

Therapeutic: antineoplastics

Pharmacologic: drug-antibody conjugates

Indications

HER2-positive metastatic breast cancer previously

treated with trastuzumab and a taxane.

Action

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.

Therapeutic Effects: Decreased spread of metastatic

breast cancer, with improved progression-free

survival.

Pharmacokinetics

Absorption: IV administration results in complete

bioavailability.

Distribution: Unknown.

Metabolism and Excretion: DM1 is metabolized

by CYP3A4/5.

Half-life: 4 days.

TIME/ACTION PROFILE (comparative

improvement in progression-free survival)

ROUTE ONSET PEAK DURATION

IV 4–6 mos 10–12 mos 2 yr

Contraindications/Precautions

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 A

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,qlacrimation.

CV: LEFT VENTRICULAR DYSFUNCTION, hypertension, peripheral

edema. GI: HEPATOTOXICITY, constipation,q

liver enzymes, nausea, altered taste, diarrhea, dry

mouth, dyspepsia, stomatitis, vomiting. Derm: pruritus,

rash. F and E: hypokalemia. GU:pfertility. Hemat:

HEMORRHAGE, THROMBOCYTOPENIA, anemia, neutropenia.

MS: musculoskeletal pain, arthralgia,

myalgia. Neuro: peripheral neuropathy. Misc: HYPERSENSITIVITY

REACTIONS, chills, infusion-related reactions,

fever.

Interactions

Drug-Drug: Blood levels and risk of toxicity may be

qby 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,

mayqrisk of bleeding.

Route/Dosage

IV (Adults): 3.6 mg/kg every 3 wk continued until disease

progresses or unacceptable toxicity occurs.

Availability

Lyophilized powder for intravenous injection

(requires reconstitution): 100 mg/vial, 160 mg/vial.