brentuximab

(redirected from Adcetris)

brentuximab

(bren-tux-i-mab) ,

Adcetris

(trade name)

Classification

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

Indications

Treatment of Hodgkin lymphoma in patients who have failed autologous stem cell transplant (ASCT) or who have failed two prior multi-agent chemotherapies and are not candidates for ASCT.Treatment of systemic anaplastic large cell lymphoma after failure of at least one multi-agent chemotherapy.

Action

genetic implication An antibody-drug conjugate (ADC) made up three parts: an antibody specific for human CD30 (cAC10, a cell membrane protein of the tumor necrosis factor receptor), a microtubule disrupting agent monomethyl auristatin (MMAE) and a protease-cleavable linker that attaches MMAE covalently to cAC10. The combination disrupts the intracellular microtubule network causing cell-cycle arrest and apoptotic cellular death.

Therapeutic effects

Decreased spread of lymphoma.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Small amounts of MMAE that are released are metabolized by the liver and eliminated mostly by the kidneys.
Half-life: ADC—4–6 days.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
IV (ADC)unkend of infusion 3 wk
IV (MMAE)unk1–3 days3 wk

Contraindications/Precautions

Contraindicated in: Concurrent use of bleomycin (↑ risk of pulmonary toxicity); Obstetric: Pregnancy Lactation: Breast feeding should be avoided.
Use Cautiously in: Geriatric: Safety and effectiveness not established; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • anxiety (most frequent)
  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • insomia (most frequent)

Respiratory

  • cough (most frequent)
  • dyspnea (most frequent)
  • oropharyngeal pain (most frequent)

Cardiovascular

  • peripheral edema

Gastrointestinal

  • abdominal pain (most frequent)
  • constipation (most frequent)
  • ↓ appetite (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Dermatologic

  • alopecia (most frequent)
  • night sweats (most frequent)
  • pruritus (most frequent)
  • rash (most frequent)
  • dry skin

Hematologic

  • neutropenia
  • thrombocytopenia
  • anemia (most frequent)

Musculoskeletal

  • arthralgia (most frequent)
  • back pain (most frequent)
  • extremity pain (most frequent)
  • myalgia (most frequent)
  • muscle spasm

Metabolic

  • weight loss (most frequent)

Neurologic

  • progressive multifocal leukoencephalopathy (pml) (life-threatening)
  • peripheral neuropathy (most frequent)

Miscellaneous

  • infusion reactions including anaphylaxis
  • Stevens-Johnson syndrome (life-threatening)
  • tumor lysis syndrome (life-threatening)
  • fever (most frequent)
  • lymphadenopathy (most frequent)
  • chills

Interactions

Drug-Drug interaction

MMAE is both a substrate and inhibitor of the CYP3A4/5 enyzyme system.Bleomycin may ↑ risk of pulmonary toxicity; concurrent use contraindicated.Strong CYP3A4 inhibitors, including ketoconazole may ↑ levels and risk of adverse reactions.Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness.

Route/Dosage

Intravenous (Adults) 1.8 mg/kg every 3 weeks up to a maximum of 16 cycles, disease progression or unacceptable toxicity.

Availability

Lyophilized powder for IV injection (requires reconstitution): 50 mg/vial

Nursing implications

Nursing assessment

  • Monitor for signs and symptoms of peripheral neuropathy (hypoesthesia, hyperesthesia, paresthesia, discomfort, burning, neuropathic pain, weakness). For new or worsening neuropathy Grade 2 or 3, delay next dose until neuropathy improves to Grade 1 or baseline, then restart at 1.2 mg/kg.
  • Assess for signs and symptoms of infusion-related reaction, including anaphylaxis (rash, pruritus, dyspnea, swelling of face and neck). If anaphylaxis occurs, discontinue infusion immediately; do not restart. Treat other infusion-related reactions by stopping and treating symptoms. Premedicate patient prior to subsequent infusions with acetaminophen, an antihistamine, and a corticosteroid.
  • Monitor patient for tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hypophosphatemia). Risks are higher in patients with greater tumor burden and rapidly proliferating tumors; may be fatal. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
  • Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. Stevens-Johnson syndrome may develop. Treat symptomatically; may recur once treatment is stopped.
  • Assess for any new signs or symptoms that may be suggestive of PML, an opportunistic infection of the brain caused by the JC virus, that leads to death or severe disability; withhold dose and notify health care professional promptly. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of brain is infected (mental function declines rapidly and progressively, causing dementia; speaking becomes increasingly difficult; partial blindness; difficulty walking; rarely, headaches and seizures occur). Diagnosis is usually made via gadolinium-enhanced MRI and CSF analysis. Risk of PML increases with the number of infusions. Withhold brentuximab at first sign of PML.
  • Lab Test Considerations: Monitor CBC prior to each dose and more frequently in patients with Grade 3 or 4 neutropenia. Prolonged (≥1 wk) severe neutropenia may occur. Hold dose of brentuximab for Grade 3 or 4 neutropenia until resolution to baseline or Grade 2 or lower. Consider growth factor support for subsequent cycles for patients who developed Grade 3 or 4 neutropenia. Discontinue brentuximab or reduce dose to 1.2 mg/kg in patients with recurrent Grade 4 neutropenia despite use of growth factors.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Intermittent Infusion: Calculate dose and number of brentuximab vials needed. Calculate for 100 kg for patients weighing >100 kg. Reconstitute each 50 mg vial with 10.5 mL of Sterile Water for Injection for a concentration of 5 mg/mL. Direct stream to side of vial. Swirl gently; do not shake. Solution should be clear to slightly opalescent, and colorless. Do not administer solutions that are discolored or contain a precipitate. Withdraw volume of brentuximab dose from infusion bag of at least 100 mL. Diluent: 0.9% NaCl, D5W, or LR.Invert bag gently to mix. Dilute immediately into infusion bag or store solution in refrigerator; use within 24 hrs of reconstitution. Do not freeze.
  • Rate: Infuse over 30 min. Do not administer as IV push or bolus.
  • Y-Site Incompatibility: Do not administer with other products.

Patient/Family Teaching

  • Instruct patient to notify health care professional of any numbness or tingling of hands or feet or any muscle weakness.
  • Advise patient to notify health care professional immediately signs and symptoms of infection (fever of ≥100.5 F°, chills, cough, pain on urination) or infusion reactions (fever, chills, rash, breathing problems within 24 hr of infusion) occur.
  • Caution female of childbearing age to use effective contraception during therapy. Avoid pregnancy and breast feeding. If pregnancy is suspected, notify health care professional promptly.

Evaluation/Desired Outcomes

  • Decreases spread of lymphoma.
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References in periodicals archive ?
The use of ADCs in cancer therapy continues to grow, with 2018 sales of Roche's Kadcyla now exceeding US$1 billion and Adcetris US$870 million[1].
The company also highlighted ADCETRIS (brentuximab vedotin) commercialization and clinical development accomplishments and progress with its late-stage clinical programs for cancer.
Important label expansions for ADCETRIS to include previously untreated Hodgkin lymphoma approved in Japan and Europe, as well as TRINTELLIX in the U.S.
Seattle Genetics anticipates using the net proceeds from the offering to fund ongoing commercialization of Adcetris in the United States and Canada, to fund its activities in preparation for the potential commercial launch of enfortumab vedotin, if approved by the FDA, to fund its research and development efforts designed to further expand the Adcetris label and to advance its pipeline of product candidates, as well as for general corporate purposes, including working capital.
The company reported Q2 Adcetris revenue of $159M, beating consensus of $149M and reversing the trend of low single-digit quarter-over-quarter growth observed over the last three quarters, Catanzaro tells investors in a research note.
Adcetris Speeds To PTCL Approval With Two-Week Review
announced data from its ADCETRIS (brentuximab vedotin) clinical development program at the 24th Annual Congress of the European Hematology Association (EHA) taking place June 13-16 in Amsterdam; and the International Conference on Malignant Lymphoma (ICML) from June 18-22 in Lugano.
* Adcetris (brentuximab vedotin) from Seattle Genetics was approved in 2011 for treatment of Hodgkin lymphoma and anaplastic large cell lymphoma;
Also, Wright has experience of cGMP manufacture of 25 ADC projects, including the manufacture of ADCETRIS (brentuximab vedotin), a CD30-targeting ADC for the treatment of relapsed or refractory Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, which was one of the first ADCs approved.
Food and Drug Administration approval of Adcetris (brentuximab vedotin) has been expanded to include adults with untreated stage III or IV classical Hodgkin's lymphoma, the agency said Tuesday in a news release.
Seattle Genetics has been involved in ADC R&D for more than 15 years, and most conference attendees will probably be familiar with Adcetris, our first marketed product that received its first approval in 2011.
"Antibody Drug Conjugate Market-- (Drug Type -- Adcetris and Kadcyla): Market Growth, Future Prospects and Competitive Analysis, 2016-2023," the market was valued at USD 1.3 Bn in 2015, and is expected to reach USD 29.3 Bn by 2022, expanding at a CAGR of 41.7% from 2016 to 2024.