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Arzerra

  • Generic Name: ofatumumab injection
  • Brand Name: Arzerra

Arzerra (Ofatumumab Injection) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

 

Arzerra Side Effects Center

What Is Arzerra?

Arzerra (ofatumumab) Injection is a monoclonal antibody used in to treat chronic lymphocytic leukemia. Arzerra is usually given after other medications have been tried without successful treatment of symptoms.

What Are Side Effects of Arzerra?

Common side effects of Arzerra include:

Arzerra decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This side effect of Arzerra can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising or bleeding. Tell your doctor if you have the following symptoms:

  • easy bruising/bleeding,
  • pale skin,
  • unusual tiredness, or
  • signs of infection (such as fever, chills, cough, persistent sore throat).

Dosage for Arzerra

The recommended dosage and schedule of Arzerra is 12 doses administered as follows: 300 mg initial dose (Dose 1), followed 1 week later by 2,000 mg weekly for 7 doses (Doses 2 through 8), followed 4 weeks later by 2,000 mg every 4 weeks for 4 doses (Doses 9 through 12).

What Drugs, Substances, or Supplements Interact with Arzerra?

Arzerra may interact with other drugs. Tell your doctor all medications and supplements you use.

Arzerra During Pregnancy and Breastfeeding

During pregnancy, Arzerra should be used only if prescribed. It is unknown if this drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breastfeeding.

Additional Information

Our Arzerra (ofatumumab) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Arzerra Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection or up to 24 hours later. Tell your caregiver right away if you feel dizzy, tired, nauseated, light-headed, feverish, chilled, sweaty, itchy, or have a skin rash, headache, muscle pain, back pain, stomach pain, irregular heartbeats, chest tightness, trouble breathing, or swelling and irritation in your throat.

Ofatumumab may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have problems with speech, thought, vision, or muscle movement. These symptoms may start gradually and get worse quickly.

Call your doctor at once if you have:

  • pain, redness, swelling, or itching where the medicine was injected;
  • right-sided upper stomach pain, vomiting, loss of appetite, yellowing of your skin or eyes, and not feeling well;
  • a lung infection--fever, chills, cough with mucus, chest pain, feeling short of breath;
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath; or
  • signs of tumor cell breakdown--tiredness, weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, tingling in your hands and feet or around your mouth.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • side effects during an infusion;
  • irritation where an injection was given;
  • fever, low blood cell counts;
  • cold symptoms such as stuffy nose, sneezing, sore throat;
  • cough, chest tightness, trouble breathing, lung infection;
  • diarrhea, nausea;
  • rash; or
  • headache, tiredness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Arzerra (Ofatumumab Injection)

 

Arzerra Professional Information

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Previously Untreated CLL

The safety of ARZERRA was evaluated in an open-label, parallel-arm, randomized trial (Study 1) in 444 patients with previously untreated CLL. Patients were randomized to receive either ARZERRA as an intravenous infusion every 28 days in combination with chlorambucil (n = 217) or chlorambucil as a single agent (n = 227). In both arms, patients received chlorambucil 10 mg/m2 orally on Days 1 to 7 every 28 days. The infusion schedule for ARZERRA was 300 mg administered on Cycle 1 Day 1, 1,000 mg administered on Cycle 1 Day 8, and 1,000 mg administered on Day 1 of subsequent 28-day cycles. The median number of cycles of ARZERRA completed was 6.

The most common adverse reactions (≥10%) were infusion reactions and neutropenia (Table 4).

The data described in Table 4 include relevant adverse reactions occurring up to 60 days after the last dose of study medication; Table 5 includes relevant hematologic laboratory abnormalities.

Table 4. Adverse Reactions with ≥5% Incidence in Patients Receiving ARZERRA plus Chlorambucil and Also ≥2% More than Patients Receiving Chlorambucil

Adverse Reactions ARZERRA plus Chlorambucil
(N = 217)		 Chlorambucil
(N = 227)
All Grades
%		 Grade ≥3
%		 All Grades
%		 Grade ≥3
%
Infusion reactionsa 67 10 0 0
Neutropenia 27 26 18 14
Asthenia 8 <1 5 0
Headache 7 <1 3 0
Leukopenia 6 3 2 <1
Herpes simplexb 6 0 4 <1
Lower respiratory tract infection 5 1 3 <1
Arthralgia 5 <1 3 0
Upper abdominal pain 5 0 3 0
a Includes events which occurred on the day of an infusion or within 24 hours of the end of an infusion and resulted in an interruption or discontinuation of treatment. Infusion reactions may include, but are not limited to, chills, dyspnea, flushing, hypotension, nausea, pain, pruritus, pyrexia, rash, and urticaria.
b Includes oral herpes, herpes, herpes virus infection, genital herpes, and herpes simplex.

Table 5. Post-baseline Hematologic Laboratory Abnormalities Occurring with ≥5% Incidence in Patients Receiving ARZERRA plus Chlorambucil and Also ≥2% More than Patients Receiving Chlorambucil

Investigations ARZERRA plus Chlorambucil
(N = 217)		 Chlorambucil
(N = 227)
All Grades
%		 Grade ≥3
%		 All Grades
%		 Grade ≥3
%
Leukopenia 67 23 28 4
Neutropenia 66 29 56 24
Lymphopenia 52 29 20 7

Infusion Reactions

Overall, 67% of patients who received ARZERRA in combination with chlorambucil experienced one or more symptoms of infusion reactions (10% were Grade 3 or greater; none were fatal). Infusion reactions occurred most frequently during Cycle 1 (56% on Day 1 [6% were Grade 3 or greater] and 23% on Day 8 [3% were Grade 3 or greater]) and decreased with subsequent infusions. Infusion reactions led to discontinuation of treatment in 3% of patients. Serious adverse events of infusion reactions occurred in 2% of patients.

Neutropenia

Overall, 3% of patients had neutropenia as a serious adverse event, reported up to 60 days after the last dose. One patient died with neutropenic sepsis and agranulocytosis. Prolonged neutropenia occurred in 6% of patients receiving ARZERRA in combination with chlorambucil compared with 4% of patients receiving chlorambucil. Late-onset neutropenia occurred in 6% of patients receiving ARZERRA in combination with chlorambucil compared with 1% of patients receiving chlorambucil alone.

Relapsed CLL

The safety of ARZERRA in combination with fludarabine and cyclophosphamide compared with fludarabine and cyclophosphamide was evaluated in a randomized, open-label, parallel-arm, multicenter trial (Study 2) in 359 patients with relapsed CLL. Patients were randomized to receive ARZERRA as an intravenous infusion (Cycle 1: 300 mg on Day 1 and 1,000 mg on Day 8; followed by 1,000 mg on Day 1 of subsequent 28-day cycles for a maximum of 6 cycles). Standard fludarabine and cyclophosphamide therapy was administered as a 3-day course starting on the first day of each cycle, with initial dosages of 25 mg/m2 for fludarabine and 250 mg/m2 for cyclophosphamide. Table 6 includes adverse reactions occurring up to 60 days after the last dose of study medication.

The most common adverse reactions (≥10%) were infusion reactions, neutropenia, leukopenia and febrile neutropenia (Table 6).

Table 6. Adverse Reactions with ≥5% Incidence in Patients Receiving ARZERRA plus FC and Also ≥2% More than in Patients in Fludarabine and Cyclophosphamide Arm

Adverse Reactions ARZERRA plus Fludarabine and Cyclophosphamide
(N = 181)		 Fludarabine and Cyclophosphamide Arm
(N = 178)
All Grades
%		 Grade ≥3
%		 All Grades
%		 Grade ≥3
%
Infusion reactionsa 60 9 28 3
Neutropenia 55 49 39 36
Leukopenia 15 12 6 3
Febrile neutropenia 10 10 8 8
Bronchitis 6 1 4 <1
a Includes events which occurred on the day of an infusion or within 24 hours of the end of an infusion and resulted in an interruption or discontinuation of treatment. Infusion reactions may include, but are not limited to, chills, dyspnea, flushing, hypotension, nausea, pain, pruritus, pyrexia, rash, and urticaria.

Adverse reactions associated with decreased platelet counts (including but not limited to thrombocytopenia, platelet count decreased and pancytopenia) and decreased hemoglobin (including but not limited to anemia, hemoglobin decreased and pancytopenia) occurred less frequently in the ARZERRA plus fludarabine and cyclophosphamide arm than in the fludarabine and cyclophosphamide arm up to 60 days after the last dose of study treatment: 30% (all grades) and 15% (Grade ≥3) vs 38% (all grades) and 28% (Grade ≥3), respectively for decreased platelet counts; and 23% (all grades) and 10% (Grade ≥ 3) vs 33% (all grades) and 16% (Grade ≥3), respectively for decreased hemoglobin.

Infusion Reactions

On Day 1 of infusion, infusion reactions occurred in 49% (7% were >Grade 3) of patients treated with ARZERRA plus fludarabine and cyclophosphamide, compared to 16% (1% were >Grade 3) of patients treated with fludarabine and cyclophosphamide and decreased with subsequent infusions. Infusion reactions led to discontinuation of treatment in 3% of patients in the ARZERRA plus fludarabine and cyclophosphamide. Serious adverse events of infusion reactions occurred in 2% of patients in the ARZERRA plus fludarabine and cyclophosphamide compared to <1% of patients treated with fludarabine and cyclophosphamide.

Neutropenia

The proportion of patients that had Grade 3 or greater neutropenia reported up to 60 days after the last dose of study medication was higher in patients treated with ARZERRA plus fludarabine and cyclophosphamide (51%) compared to the fludarabine and cyclophosphamide arm (37%). Grade 3 or greater neutropenic sepsis occurred in 2 patients (1%) treated with ARZERRA plus fludarabine and cyclophosphamide vs. 3 patients (2%) in the fludarabine and cyclophosphamide arm. Prolonged neutropenia occurred in 18 patients (10%) treated with ARZERRA plus fludarabine and cyclophosphamide vs. 20 patients (11%) in the fludarabine and cyclophosphamide arm. Late-onset neutropenia occurred in 13 patients (7%) treated with ARZERRA plus fludarabine and cyclophosphamide vs. 5 patients (3%) in the fludarabine and cyclophosphamide arm.

During the period between the first dose and 60 days after last dose there were five (3%) patients who died in the ARZERRA plus fludarabine and cyclophosphamide arm and ten (6%) patients who died in the fludarabine and cyclophosphamide arm.

Extended Treatment In CLL

The safety of ARZERRA was evaluated in an open-label, parallel-arm, randomized trial (Study 3) in 474 patients who had responded to therapy for their recurrent or progressive disease. Patients were randomized to receive ARZERRA as an intravenous infusion every 8 weeks or observation. The infusion schedule for ARZERRA was 300 mg on Day 1 followed 1 week later by 1,000 mg on Day 8 followed 7 weeks later by 1,000 mg and every 8 weeks thereafter for up to a maximum of 2 years. The data described in Table 7 include relevant adverse reactions occurring up to 60 days after the last dose of study medication (last visit for observation arm). The most common adverse reactions (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection (Table 7).

Table 7. Adverse Reactions with ≥5% Incidence in Patients Receiving ARZERRA and Also ≥2% More than in Patients in Observation Arm

Adverse Reactions ARZERRA
(N = 237)		 Observation Arm
(N = 237)
All Grades
%		 Grade ≥3
%		 All Grades
%		 Grade ≥3
%
Infusion reactionsa 46 4 - -
Neutropenia 24 22 9 8
Upper respiratory tract infection 19 1 9 0
Bronchitis 9 <1 7 <1
Pneumonia 8 5 5 3
Influenza 6 0 3 0
Herpes zoster 5 <1 3 <1
Insomnia 5 <1 2 0
Back pain 5 0 3 0
Hypogammaglobulinemia 5 <1 <1 <1
a Includes events which occurred on the day of an infusion or within 24 hours of the end of an infusion and resulted in an interruption or discontinuation of treatment. Infusion reactions may include, but are not limited to, chills, dyspnea, flushing, hypotension, nausea, pain, pruritus, pyrexia, rash, and urticaria.

Infusion Reactions

Infusion reactions occurred in 25% of patients on the day of Infusion 1 (300 mg) and decreased with subsequent infusions (between 2% to 10%).

Infections

A total of 154 patients (65%) treated with ARZERRA compared with 120 patients (51%) in the observation arm experienced bacterial, viral, or fungal infections. The incidence of serious infections, however, was similar for patients treated with ARZERRA (20%) and the observation arm (18%). The proportions of fatal infections in patients treated with ARZERRA and in the observation arm were 2% and 3% respectively.

Neutropenia

The proportion of patients that had Grade 3 or greater neutropenia reported up to 60 days after the last dose of study medication was higher in patients treated with ARZERRA (22%) compared with the observation arm (8%). There were no cases of neutropenic sepsis reported with ARZERRA. Prolonged neutropenia occurred in 13 patients (5%) treated with ARZERRA and in 5 patients (2%) in the observation arm. Late-onset neutropenia occurred in 2 patients (<1%) treated with ARZERRA and 1 patient (<1%) in the observation arm.

During the period between the first dose and 60 days after last dose there were two (1%) patients in the ofatumumab group who died due to adverse events and five (2%) patients in the observation group.

Refractory CLL

The safety of monotherapy with ARZERRA was evaluated in 181 patients with relapsed or refractory CLL in 2 open-label, non-randomized, single-arm studies. In these studies, ARZERRA was administered at 2,000 mg beginning with the second dose for 11 doses (Study 4 [n = 154]) or 3 doses (Study 5 [n = 27]).

The data described in Table 8 and other sections below are derived from 154 patients in Study 4. All patients received 2,000 mg weekly from the second dose onward. Ninety percent (90%) of patients received at least 8 infusions of ARZERRA and 55% received all 12 infusions. The median age was 63 years (range: 41 to 86 years), 72% were male, and 97% were white.

In refractory CLL, the most common adverse reactions (≥10%) were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections (Table 8). The most common serious adverse reactions were infections (including pneumonia and sepsis), neutropenia, and pyrexia. Infections were the most common adverse reactions leading to drug discontinuation.

Table 8. Incidence of All Adverse Reactions Occurring in ≥5% of Patients and in the Fludarabine- and Alemtuzumab-refractory Subset

Adverse Reaction Total Population
(N = 154)		 Fludarabine- and Alemtuzumab-refractory
(N = 59)
All Grades
%		 Grade ≥3
%		 All Grades
%		 Grade ≥3
%
Pneumoniaa 23 14 25 15
Pyrexia 20 3 25 5
Cough 19 0 19 0
Diarrhea 18 0 19 0
Anemia 16 5 17 8
Fatigue 15 0 15 0
Dyspnea 14 2 19 5
Rashb 14 <1 17 2
Bronchitis 11 <1 19 2
Nausea 11 0 12 0
Upper respiratory tract infection 11 0 3 0
Edema peripheral 9 <1 8 2
Back pain 8 1 12 2
Chills 8 0 10 0
Nasopharyngitis 8 0 8 0
Sepsisc 8 8 10 10
Urticaria 8 0 5 0
Insomnia 7 0 10 0
Headache 6 0 7 0
Herpes zoster 6 1 7 2
Hyperhidrosis 5 0 5 0
Hypertension 5 0 8 0
Hypotension 5 0 3 0
Muscle spasms 5 0 3 0
Sinusitis 5 2 3 2
Tachycardia 5 <1 7 2
a Includes pneumonia, lung infection, lobar pneumonia, and bronchopneumonia.
b Includes rash, rash macular, and rash vesicular.
c Includes sepsis, neutropenic sepsis, bacteremia, and septic shock.

Infusion Reactions

Infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg), 29% on the day of the second infusion (2,000 mg), and less frequently during subsequent infusions.

Infections

A total of 108 patients (70%) experienced bacterial, viral, or fungal infections. A total of 45 patients (29%) experienced Grade 3 or greater infections, of which 19 (12%) were fatal. The proportion of fatal infections in the fludarabine- and alemtuzumab-refractory group was 17%.

Neutropenia

Of 108 patients with normal neutrophil counts at baseline, 45 (42%) developed Grade 3 or greater neutropenia. Nineteen (18%) developed Grade 4 neutropenia. Some patients experienced new onset Grade 4 neutropenia >2 weeks in duration.

Immunogenicity

There is a potential for immunogenicity with therapeutic proteins such as ofatumumab. Serum samples from more than 926 patients with CLL were tested during and after treatment for antibodies to ARZERRA. Formation of anti-ofatumumab antibodies was observed in less than 1% of patients with CLL after treatment with ofatumumab.

Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to ARZERRA with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ARZERRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infusion-Related Cardiac Events

Cardiac arrest

Mucocutaneous Reactions

Stevens-Johnson syndrome, porphyria cutanea tarda

Read the entire FDA prescribing information for Arzerra (Ofatumumab Injection)

&Copy; Arzerra Patient Information is supplied by Cerner Multum, Inc. and Arzerra Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.