Important Safety Information

WARNING HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY Hepatitis B virus (HBV) reactivation can occur in patients receiving CD20-directed cytolytic antibodies, includi…+

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Important Safety Information

  • In combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate
  • In combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL
  • For extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL
  • For the treatment of patients with CLL refractory to fludarabine and alemtuzumab

 

Dosing & Administration

Dosing in FA-Refractory CLL

 ARZERRA Is Administered as 12 Infusions Over a 24-Week Period1




  • Do not administer as an intravenous push or bolus or as a subcutaneous injection
  • The recommended dosage and schedule is 12 doses administered as follows:
    • 300-mg initial dose (Dose 1), followed 1 week later by
    • 2000 mg weekly for 7 doses (Doses 2 through 8), followed 4 weeks later by
    • 2000 mg every 4 weeks for 4 doses (Doses 9 through 12) 



Administration for FA-Refractory CLL

Premedicate 30 Minutes to 2 Hours Prior to Each Dose1

  • ARZERRA can cause serious, including fatal, infusion reactions. Premedicate before each infusion
  • Infusion reactions may occur despite premedication

aCorticosteroid may be reduced or omitted for subsequent infusions if a Grade ≥3 infusion-related adverse event reaction did not occur with the preceding infusion(s)
bPrednisolone may be given at reduced dose of 50 mg to 100 mg (or equivalent) if a Grade ≥3 infusion-related adverse event did not occur with Infusion 9. 

Administration1

  • Do not administer as an intravenous push or bolus or as a subcutaneous injection
  • Do not mix ARZERRA with, or administer as an infusion with, other medicinal products
  • Administer using an infusion pump and an administration set
  • Prepare all doses in 1000 mL of 0.9% Sodium Chloride Injection, USP
  • Initiate infusion of Dose 1 at a rate of 3.6 mg/hour (12 mL/hour) and Dose 2 at a rate of 24 mg/hour (12 mL/hour). Initiate infusion of Doses 3-12 at a rate of 50 mg/hour (25 mL/hour)
  • In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes as described in Table 2 of the Prescribing Information. Do not exceed the infusion rates in the table below

 
Recommended Infusion Rates for ARZERRA1 

  • Median infusion times1:
    • Infusions 1 and 2 (300 mg and 2000 mg): Median duration of infusions = 6.8 hours
    • Subsequent infusions of 2000 mg:  Median durations of infusions = 4.2 to 4.4 hours 

Infusion rate for ARZERRA

  • In the absence of an infusion-related adverse event, the rate of infusion may be increased every 30 minutes as described in the table above. Do not exceed the infusion rates in the table above.




Dose Modifications for IRs in FA-Refractory CLL

Dose Modifications for ARZERRA1

  • Interrupt infusion for infusion reactions of any severity
  • Treatment can be resumed at the discretion of the treating physician. The following infusion rate modifications can be used as a guide
  • If the infusion reaction resolves or remains Grade ≤2, resume infusion with the following modifications according to the initial grade of the infusion reaction:
    • Grade 1 or 2: infuse at one-half of the previous infusion rate
    • Grade 3 or 4: infuse at a rate of 12 mL/hour
  • After resuming the infusion, the infusion rate may be increased according to the table of recommended infusion rates above based on patient tolerance
  • Consider permanent discontinuation of ARZERRA if the severity of the infusion reaction does not resolve to Grade ≤2 despite adequate clinical intervention
  • Permanently discontinue therapy for patients who develop an anaphylactic reaction to ARZERRA

 

Video: ARZERRA Dosing & Administration

View the ARZERRA Dosing & Administration Video

Learn about the dosing and administration of ARZERRA for both FA-refractory and first-line CLL in this lively animated video. For more information on dosing and administration, please see the ARZERRA Prescribing Information, download a copy of the ARZERRA Dosing & Administration Guide, or contact Novartis Oncology Medical Information at 1-844-ONC-INFO (1-844-662-4636) or https://medinfo.novartispharmaceuticals.com/

Reference: 1. Arzerra [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2016.

INDICATIONS for ARZERRA® (ofatumumab)

  • In combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate
  • In combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL
  • For extended treatment of patients who are in complete or partial response after at least 2  lines of therapy for recurrent or progressive CLL
  • For the treatment of patients with CLL refractory to fludarabine and alemtuzumab

IMPORTANT SAFETY INFORMATION for ARZERRA® (ofatumumab)

WARNING: HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

  • Hepatitis B virus (HBV) reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ARZERRA, in some cases resulting in fulminant hepatitis, hepatic failure, and death

  • Progressive multifocal leukoencephalopathy (PML) resulting in death can occur in patients receiving CD20-directed cytolytic antibodies, including ARZERRA

 

Infusion Reactions

  • ARZERRA can cause serious, including fatal, infusion reactions manifesting as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac events, back pain, abdominal pain, pyrexia, rash, urticaria, angioedema, cytokine release syndrome, and anaphylactoid/anaphylactic reactions
  • Administer ARZERRA in an environment where facilities to adequately monitor and treat infusion reactions are available. Premedicate with acetaminophen, an antihistamine, and a corticosteroid. Infusion reactions may occur despite premedication
  • Interrupt ARZERRA for infusion reactions of any severity and initiate appropriate medical treatment. If an anaphylactic reaction occurs, immediately and permanently discontinue ARZERRA

Hepatitis B Virus Reactivation

  • Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has occurred in patients treated with ARZERRA 
  • Screen all patients for HBV infection before initiating ARZERRA
  • Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following treatment with ARZERRA. HBV reactivation has been reported for at least 12 months following completion of therapy
  • In ARZERRA-treated patients who develop reactivation of HBV, immediately discontinue ARZERRA and any concomitant chemotherapy, and institute appropriate treatment

HBV Infection

  • Fatal infection due to hepatitis B in patients who have not been previously infected has been observed with ARZERRA. Monitor patients for clinical and laboratory signs of hepatitis

Progressive Multifocal Leukoencephalopathy

  • Progressive multifocal leukoencephalopathy (PML) resulting in death has occurred with ARZERRA. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms
  • If PML is suspected, discontinue ARZERRA and initiate evaluation for PML, including neurology consultation

Tumor Lysis Syndrome

  • Tumor lysis syndrome (TLS), including the need for hospitalization, has occurred in patients treated with ARZERRA. Patients with high tumor burden and/or high circulating lymphocyte counts (>25 x 109/L) are at greater risk
  • Consider TLS prophylaxis with antihyperuricemics and hydration prior to infusion of ARZERRA
  • For treatment of TLS, administer aggressive intravenous hydration and antihyperuricemic agents, correct electrolyte abnormalities, and monitor renal function

Cytopenias

  • Severe cytopenias, including neutropenia, thrombocytopenia, and anemia, can occur with ARZERRA. Pancytopenia, agranulocytosis, and fatal neutropenic sepsis have occurred in patients who received ARZERRA in combination with chlorambucil. Grade 3/4 late-onset neutropenia and/or prolonged neutropenia were reported in ARZERRA-treated patients
  • Monitor complete blood counts at regular intervals during and after conclusion of therapy, and increase the frequency of monitoring in patients who develop grade 3/4 cytopenias

Immunizations

  • Do not administer live viral vaccines to patients who have recently received ARZERRA

Most Common Adverse Reactions

  • Previously untreated CLL: (≥10%, all grades) were infusion reactions (67% for ARZERRA plus chlorambucil vs 0% for chlorambucil) and neutropenia (27% vs 18%)
  • Extended treatment therapy in CLL: Common adverse reactions (≥10%) were infusion reactions, neutropenia, and upper respiratory infection 
  • Relapsed CLL: Common adverse reactions (≥10%) were infusion reactions, neutropenia, febrile neutropenia, and leukopenia
  • In the single-arm refractory CLL clinical trial, the most common adverse reactions (≥10%, all grades) were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. The most common serious adverse reactions were infections (including pneumonia and sepsis), neutropenia, and pyrexia

Laboratory Abnormalities

  • In the previously untreated CLL clinical trial, postbaseline hematologic laboratory abnormalities (all grades) occurring with ≥5% incidence in patients receiving ARZERRA plus chlorambucil, and also ≥2% more than patients receiving chlorambucil, were leukopenia (67% for ARZERRA plus chlorambucil vs 28% for chlorambucil), neutropenia (66% vs 56%), and lymphopenia (52% vs 20%)

Please see full Prescribing Information, including Boxed WARNING, for ARZERRA.

 

*Assessed by a blinded Independent Review Committee (IRC) using the International Workshop on Chronic Lymphocytic Leukemia updated National Cancer Institute–sponsored Working Group (NCI-WG) guidelines (1996).1

The efficacy of ARZERRA was studied in a single-arm, multicenter trial of 154 patients with CLL refractory to fludarabine and alemtuzumab (n=59).1 

CI=confidence interval; CLL=chronic lymphocytic leukemia; FA=fludarabine and alemtuzumab.

Reference: 1. Arzerra [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2016.