ado-trastuzumab

High Alert

HER2-positive metastatic breast cancer in patients previously treated with trastuzumab and a taxane who have either received prior therapy for metastatic disease or developed disease recurrence during or within 6 mo of completing adjuvant therapy.
Adjuvant treatment of HER2-positive early breast cancer in patients who have residual invasive disease after neoadjuvant taxane and trastuzumab-based therapy.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Interstitial lung disease or pneumonitis;
OB: Pregnancy;
Lactation: Lactation.

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 in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: HF, hypertension, peripheral edema

Derm: pruritus, rash

EENT: ↑lacrimation, blurred vision, conjunctivitis, dry eyes

F and E: hypokalemia

GI: ↑liver enzymes, constipation, nausea, altered taste, diarrhea, dry mouth, dyspepsia, HEPATOTOXICITY, stomatitis, vomiting

GU: ↓fertility

Hemat: anemia, HEMORRHAGE, neutropenia, THROMBOCYTOPENIA

MS: musculoskeletal pain, arthralgia, myalgia

Neuro: fatigue, headache, peripheral neuropathy, dizziness, insomnia, weakness

Resp: cough, INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS

Misc: chills, fever, HYPERSENSITIVITY REACTIONS, infusion-related reactions

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including atazanavir, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, and voriconazole, may ↑ levels and risk of toxicity; avoid concurrent use.
Concurrent use of anticoagulants or antiplatelet agents, especially during the first cycle, may ↑ risk of bleeding.

Availability ⬆ ⬇

Lyophilized powder for injection: 100 mg/vial; 160 mg/vial

Route/Dosage ⬆ ⬇

Should not be used interchangeably with trastuzumab.

Metastatic Breast Cancer

IV (Adults ): 3.6 mg/kg every 3 wk until disease progression or unacceptable toxicity.

Early Breast Cancer

IV (Adults ): 3.6 mg/kg every 3 wk (21-day cycle) for a total of 14 cycles unless there is disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: drug-antibody conjugates

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/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 mo	10–12 mo	2 yr

Patient/Family Teaching ⬆ ⬇

Explain purpose of medication to patient. If dose is missed, administer as soon as possible; do not wait until next scheduled dose. Adjust schedule to maintain 3-wk interval between doses.
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 hr, 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: May cause fetal harm. Advise women of reproductive potential to use a highly effective method of contraception during therapy and for ≥7 mo after last dose. Advise men with a female partner of reproductive potential to use a highly effective method of contraception during therapy and for ≥4 mo after last dose. Notify health care professional promptly if pregnancy is suspected and avoid breastfeeding for ≥7 mo after last dose. Encourage women who have been exposed to ado-trastuzumab during pregnancy, either directly or through seminal fluid to immediately report exposure to Genentech Adverse Event Line at 1-888-835-2555. May impair fertility in all patients.

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Indications ⬇