ado-trastuzumab emtansine

(redirected from Kadcyla)

ado-trastuzumab emtansine

(ado tras-tooz-doo-mab em-tan-seen) ,

Kadcyla

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: drug antibody conjugates
Pregnancy Category: D

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)

ROUTEONSETPEAKDURATION
IV4–6 mos10–12 mos2 yr

Contraindications/Precautions

Contraindicated in: Interstitial lung disease or pneumonitis;Concurrent use of strong inhibitors of CYP3A4; Lactation: Breast feeding should be avoided; Obstetric: May cause fetal harm.
Use Cautiously in: Underlying cardiovascular or pulmonary disease, including dyspnea at rest; Obstetric: Patients with reproductive potential (contraception required during and for 6 mos following treatment); Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • headache (most frequent)
  • dizziness
  • insomnia
  • weakness

Respiratory

  • pulmonary toxicity (life-threatening)
  • cough

Ear, Eye, Nose, Throat

  • blurred vision
  • conjuncitivitis
  • dry eyes
  • ↑ lacrimation

Cardiovascular

  • left ventricular dysfunction (life-threatening)
  • hypertension
  • peripheral edema

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • constipation (most frequent)
  • ↑ liver enzymes (most frequent)
  • nausea (most frequent)
  • altered taste
  • diarrhea
  • dry mouth
  • dyspepsia
  • stomatitis
  • vomiting

Dermatologic

  • pruritus
  • rash

Fluid and Electrolyte

  • hypokalemia

Hematologic

  • thrombocytopenia (life-threatening)
  • anemia (most frequent)
  • ne
  • neutropenia

Musculoskeletal

  • musculoskeletal pain (most frequent)
  • arthralgia
  • myalgia

Neurologic

  • peripheral neuropathy

Miscellaneous

  • hypersensitivity reactions (life-threatening)
  • chills
  • infusion-related reactions
  • fever

Interactions

Drug-Drug interaction

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, telithromycin, and voriconazole, and should be avoided, waiting 3 half-lives of inhibitor to start treatment.

Route/Dosage

Intravenous (Adults) 3.6 mg/kg once every 3 wk continued until disease progresses or unacceptable toxicity occurs. Dose modifications (reduction or temporary discontinuation) required for ↑ transaminases, hyperbilirubinemia, left ventricular dysfunction, peripheral neuropathy or thrombocytopenia.

Availability

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

Nursing implications

Nursing assessment

  • Evaluate left ventricular function in all patients prior to and every 3 months 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.
  • Lab Test Considerations: genetic implication 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.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • 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 (see ).
  • 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 solution. 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 0.22 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.
  • Y-Site Incompatibility: Do not mix or administer with other medications.

Patient/Family Teaching

  • 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.
  • Ado-trastuzumab can cause fetal harm. Advise male and female patient to use a highly effective method (IUD, hormonal contraceptive, tubal ligation, partner's vasectomy) of contraception during and for at least 6 months after last dose. Instruct patient to notify health care professional promptly if pregnancy is suspected or if breast feeding. 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.

Evaluation/Desired Outcomes

  • Decreased spread of metastatic breast cancer.
References in periodicals archive ?
The currently marketed antibody drug conjugate drugs are Adcetris (Seattle Genetics) and Kadcyla (Genentech/Roche) followed by several Antibody Drug Conjugates (ADCs) in pipeline showcase the potential for innovations in this market.
Four months ago, after exhausting the treatments available in Northern Ireland, friends raised PS22,000 in just 48 hours to buy the drug Kadcyla.
Key Market Movements: * North America presently dominates the overall market and is also projected to experience the fastest growth throughout the forecast period * The recent market entry of novel drugs including Perjeta, a targeted therapy; Kadcyla, a human antibody-drug conjugate; and Halaven, a novel chemotherapeutic agent have boosted the overall growth of breast cancer treatment market * The companies have been able to develop efficient and commercially successful products by studying pathophysiology of breast cancer in detail, e.
The mum of four - who fought for life-extending drug Kadcyla to be made available for all in Scotland who need it - is making the most out of every moment in life after being diagnosed with secondary breast cancer in 2014.
HEALTH Secretary Vaughan Gething has announced that breast cancer drug Kadcyla, will be available on the Welsh NHS.
As a result, the drug approvals body, Nice, has recommended that Kadcyla, full name Trastuzumab emtansine, should be made available.
The National Institute for Health and Care Excellence (Nice) rejected Kadcyla on cost grounds in 2015 but a deal has now been struck between NHS England and manufacturer Roche, backed by Nice, to make the drug available to around 1,200 women per year in England.
Kadcyla, which has been shown to extend the lives of patients by an average of six months, was previously rejected by the health service on cost grounds.
ImmunoGen's ADC technology is used in Roche's marketed product, Kadcyla, in three other clinical-stage ImmunoGen product candidates, and in programs in development by partners Amgen, Bayer, Biotest, CytomX, Lilly, Novartis, Sanofi and Takeda.
Women with incurable breast cancer are to get breakthrough drug Kadcyla after the Scottish Medicines Consortium approved it for the NHS.
Kadcyla (Trastuzumab emtansine) was approved to treat HER2 positive metastatic breast cancer, an aggressive, advanced form of breast cancer.
These advancements include improvements in linking technologies, which has helped in the development of drugs, such as ADCETRIS and Kadcyla.