ofatumumab

(redirected from Arzerra)

ofatumumab

(oh-fa-too-moo-mab) ,

Arzerra

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: monoclonal antibodies
Pregnancy Category: C

Indications

Chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.

Action

A monoclonal antibody that specifically binds to CD20 molecule found on the surface of B lymphocytes, resulting in B-cell lysis.

Therapeutic effects

↓ numbers of leukemic cells in CLL.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: 14 days (range: 2.3–61.5 days).

Time/action profile

ROUTEONSETPEAKDURATION
IVend of infusionunknown7 days

Contraindications/Precautions

Contraindicated in: None noted.
Use Cautiously in: History of hepatitis B infection (may reactivate); Obstetric: Use only if potential benefit to mother justifies potential risk to fetus; Lactation: Lactation; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • progressive multifocal leukoencephalopathy (PML) (life-threatening)
  • weakness

Cardiovascular

  • peripheral edema

Gastrointestinal

  • (life-threatening)
  • intestinal obstruction (life-threatening)
  • reactivation of hepatitis b (life-threatening)

Dermatologic

  • sweating

Hematologic

  • anemia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Musculoskeletal

  • back pain
  • muscle spasm

Miscellaneous

  • hepatitis b reactivation (life-threatening)
  • Infection
  • infusion reactions
  • chills
  • fever
  • tumor lysis syndrome

Interactions

Drug-Drug interaction

May ↓ antibody response to and ↑ risk of adverse reactions from live-virus vaccines.

Route/Dosage

Intravenous (Adults) 300 mg initial initially, followed 1 wk later by 2000 mg weekly for 7 doses, followed 4 wk later by 2000 mg every 4 wk for 4 doses (total regimen is 12 doses).

Availability

Solution for IV administration (requires further dilution): 20 mg/mL

Nursing implications

Nursing assessment

  • Monitor for infusion reactions (bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema); may occur more frequently with first 2 infusions. Adminster in facilities equipped to monitor and treat infusion reactions. Institute medical management for severe infusion reactions. Interrupt infusion for infusion reactions of any severity. For Grade 4 reactions, do not resume infusion. For Grade 1, 2, or 3, if infusion reaction resolves or remains less than or equal to Grade 2, resume infusion at one-half of previous infusion rate if Grade 1 or 2, or at a rate of 12 mL/hr if Grade 3. After resuming, infusion rate may be ↑ as described under rate, as tolerated.
  • Assess for new signs or symptoms suggestive of PML, an opportunistic infection of the brain caused by the JC virus, leading to death or severe disability; withhold dose and notify health care professional promptly. Monitor during therapy and for at least 6 months following discontinuation. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of the 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 ofatumumab at first sign of PML.
  • Screen patients at high risk for hepatitis B virus (HBV) infection before initiating therapy. Monitor carriers of HBV for clinical and laboratory signs during and for at least 12 mo following discontinuation of therapy. Discontinue ofatumumab in patients who develop viral hepatitis or reactivation of viral hepatitis and institute appropriate treatment.
  • 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, hydrate patient, administer antihyperuricemic agents, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
  • Lab Test Considerations: Monitor CBC and platelet counts regularly during therapy and ↑ frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. May cause prolonged (≥1 wk) severe neutropenia and thrombocytopenia.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Premedicate 30 min-2 hr prior to each dose with acetaminophen PO 1000 mg, PO or IV antihistamine (cetirizine 10 mg or equivalent), and IV corticosteroid (prednisolone 100 mg or equivalent). Do not reduce corticosteroid dose for Doses 1, 2, and 9. Corticosteroid dose may be reduced for doses 3–8 and 10–12. Doses 3–8: Gradually reduce corticosteroid dose with each infusion if a reaction ≥Grade 3 did not occur with preceeding does. Doses 10–12: Administer prednisolone 50–100 mg or equivalent if a reaction ≥Grade 3 did not occur with dose 9.
  • Intravenous Administration
  • pH: 6.5.
  • Intermittent Infusion: Diluent: Dilute all doses in 1000 mL of 0.9% NaCl in a polyolefin bag. For 300 mg dose: Withdraw and discard 15 mL from 0.9% NaCl bag. Withdraw 5 mL from each of 3 ofatumumab vials and add to 0.9% NaCl bag. For 2000 mg dose: Withdraw and discard 100 mL from 0.9% NaCl bag. Withdraw 5 mL from each of 20 ofatumumab vials and add to 0.9% NaCl bag. Do not shake; mix diluted solution by gentle inversion. Solution is clear and colorless, and may contain a small amount of visible translucent-to-white, amorphous particles; do not administer if discolored, cloudy, or if foreign matter is present Refrigerate solution, do not freeze; protect vials from light. Start infusion within 12 hr of preparation; discard after 24 hr.
  • Rate: Administer through in-line filter supplied with medication using an infusion pump and PVC infusion set. Flush IV line with 0.9% NaCl before and after each dose. Do not administer as a IV push or bolus. Initiate infusion for Dose 1 at 3.6 mg/hr (12 mL/hr), Dose 2 at 24 mg/hr (12 mL/hr), Doses 3–12 at 50 mg/hr (25 mL/hr). Rate for Doses 1 and 2 may be ↑ every 30 min to 25, 50, 100, and 200 mL/hr if no infusional toxicity occurs. Rate for Doses 3–12 may be ↑ every 30 min to 50, 100, 200, and 400 mL/hr if no infusional toxicity occurs.
  • Y-Site Incompatibility: Do not mix with or infuse with other products.

Patient/Family Teaching

  • Explain the purpose of ofatumumab to patient and caregiver.
  • Advise patient to avoid live viral vaccines during therapy.
  • Advise patient to notify health care professional immediately if signs and symptoms of infusion reactions (fever, chills, rash, breathing problems) occur within 24 hr of infusion or if bleeding, PML (progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes). bruising, petechiae, pallor, worsening weakness, fatigue, cough, infection, confusion, dizziness, loss of balance, difficulty talking or walking, vision problems, yellow discoloration of skin or eyes, new or worsening abdominal pain or nausea occur.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
  • Emphasize the need for periodic blood count monitoring.

Evaluation/Desired Outcomes

  • ↓ numbers of leukemic cells in CLL.
References in periodicals archive ?
Arzerra Phase III Study Meets Primary Endpoint Of PFS In Relapsed CLL
SeeNews) - Nov 8, 2012 - Danish biotech firm Genmab A/S (CPH:GEN) saw its loss widen in the third quarter of 2012, yet raised its revenue guidance due to better-than-expected sales of cancer drug Arzerra (ofatumumab).
The companies said an injectable version of Arzerra should be more convenient for patients and have fewer side effects.
Chemotherapeutic agents approved in 2009 * Brand Generic name name Indication Afinitor Everolimus Treatment of advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib Arzerra Ofatumumab Treatment of chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab Folotyn Pralatrexate Treatment of relapsed or refractory peripheral T-cell lymphoma Istodax Romidepsin Treatment of cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy Votrient Pazopanib Treatment of advanced renal cell carcinoma * From references 51-55.
America's Food and Drug Administration has approved Arzerra, a leukaemia treatment that will be aimed at patients who have failed to respond to other therapies.
Latest advances in hematology treatments for CML with Tasigna, CLL with Arzerra, multiple myeloma with Farydak, and polycythemia vera with Jakavi
Founded in 1999, the company currently has one marketed antibody, Arzerra (ofatumumab) for the treatment of certain chronic lymphocytic leukemia indications and daratumumab in clinical development for multiple myeloma and non-Hodgkin's lymphoma, in addition to other clinical programs, and an innovative pre-clinical pipeline.
The other three drugs approved to treat CLL that received breakthrough designations are Gazyva (obinutuzumab) in November 2013, Arzerra (ofatumumab) in April 2014 and Zydelig (idelalisib) in July 2014.
The FDA approved Gazyva (obinutuzumab) in November 2013, Imbruvica (ibrutinib) in February 2014 and a new use for Arzerra (ofatumumab) in April 2014 to treat CLL.
GlaxoSmithKline plc and Genmab A/S announced today that the European Commission (EC) has granted marketing authorisation for a new indication for the use of Arzerra (ofatumumab), a human monoclonal antibody against CD20, in combination with chlorambucil or bendamustine for the treatment of patients with chronic lymphocytic leukaemia (CLL) who have not received prior therapy and who are not eligible for fludarabine-based therapy.