Arzerra

Name: Arzerra

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Ofatumumab Interactions

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using ofatumumab. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Other drugs may interact with ofatumumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Arzerra Overview

Arzerra is a prescription medication used to treat patients with leukemia. Arzerra belongs to a group of drugs called monoclonal antibodies, which work by killing cancer cells.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of Arzerra include cough, diarrhea, fatigue, and rash.

Arzerra can also cause dizziness. Do not drive or operate heavy machinery until you know how Arzerra affects you.

Side Effects of Arzerra

Serious side effects have been reported with Arzerra. See the "Arzerra Precautions" section.

Common side effects of Arzerra include:

  • pneumonia
  • fever
  • cough
  • diarrhea
  • anemia
  • fatigue
  • difficulty breathing
  • rash
  • nausea
  • bronchitis
  • upper airway infections
  • muscle spasms

This is not a complete list of Arzerra side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Arzerra and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Arzerra crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Arzerra.

Arzerra Usage

Take Arzerra exactly as prescribed.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Pharmacology

Mechanism of Action

Anti-CD20 human monoclonal antibody that inhibits B-cell activation in early stages

Pharmacokinetics

Half-Life: 14 days (mean between 4th-12th infusions)

Cmax: 63 mcg/mL (after 1st dose); 1482 mcg/mL (after 8th dose); 881 mcg/mL (after 12th dose)

Vdss: 3.2 L (after 1st dose); 5.1 L (after 8th dose); 4.7 L after 12th dose

Clearance: 0.01 L/hr (mean clearance between 4th-12th infusions)

Ofatumumab side effects

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. Tell your caregiver right away if you feel dizzy, nauseated, light-headed, confused, itchy, tingly, or have chest pain, jaw or arm pain, back pain, stomach pain, wheezing, chest tightness, or trouble breathing. These reactions can occur during the injection or within 24 hours afterward.

Call your doctor right away if you have signs of a serious brain infection: change in your mental state, decreased vision, weakness on one side of your body, or problems with speech or walking. These symptoms may start gradually and get worse quickly.

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

Call your doctor at once if you have:

  • fever, chills, cough with yellow or green mucus;

  • stabbing chest pain, wheezing, feeling short of breath;

  • liver problems--nausea, upper stomach pain, itching, tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  • low blood cell counts--fever, chills, flu-like symptoms, swollen gums, mouth sores, skin sores, rapid heart rate, pale skin, easy bruising, unusual bleeding, feeling light-headed; or

  • signs of tumor cell breakdown--lower back pain, blood in your urine, little or no urination; numbness or tingly feeling around your mouth; muscle weakness or tightness; fast or slow heart rate, weak pulse, feeling short of breath; confusion, fainting.

Common side effects may include:

  • fever, cough, flu symptoms;

  • cold symptoms such as stuffy nose, sneezing, sore throat;

  • trouble breathing;

  • diarrhea, nausea;

  • mild rash; or

  • tired feeling.

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.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Adverse reactions

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

  • Infusion Reactions [see Warnings and Precautions (5.1)]
  • Hepatitis B Virus Reactivation [see Warnings and Precautions (5.2)]
  • Hepatitis B Virus Infection [see Warnings and Precautions (5.3)]
  • Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.4)]
  • Tumor Lysis Syndrome [see Warnings and Precautions (5.5)]
  • Cytopenias [see Warnings and Precautions (5.6)]

     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
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.

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

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
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

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

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
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.
Arzerra
(N = 237)
Observation Arm
(N = 237)
Adverse Reactions 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

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
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.

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

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

Before taking this medicine

Arzerra increases the risk of a serious viral infection of the brain that can lead to disability or death. This risk is higher if you have a weak immune system or are receiving certain medicines.

To make sure Arzerra is safe for you, tell your doctor if you have:

  • an active infection;

  • hepatitis; or

  • a history of liver disease or hepatitis B.

If you have certain risk factors for hepatitis B, the virus could become active again while you are using Arzerra and for up to several months after you stop using it. This has resulted in liver failure or death in some people using this medicine. Your doctor will perform blood tests to make sure you do not have conditions that may cause you to develop hepatitis B.

Using Arzerra during pregnancy could affect the immune system of the unborn baby. Tell your doctor if you are pregnant or if you become pregnant while using this medicine.

It is not known whether ofatumumab passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

How is Arzerra given?

Arzerra is injected into a vein through an IV. A healthcare provider will give you this injection. Ofatumumab must be given slowly through an IV infusion, and one dose can take up to several hours to complete.

Arzerra is usually given in a treatment cycle over several weeks, beginning with one infusion per week. Then you will receive your infusions less often, depending on the type of CLL for which you are being treated.

Your dosing schedule may change with further doses. Your doctor will determine how long to treat you with Arzerra.

You will be given other IV or oral (by mouth) medications to prevent certain side effects of Arzerra. You may need to start using these medications up to 2 hours before the start of your ofatumumab infusion.

You may also need to take antiviral medications if you are found to have any risk factors for hepatitis B. Follow your doctor's dosing instructions very carefully. Arzerra can cause hepatitis B to come back or get worse. You will need frequent blood tests to check your liver function.

Arzerra can have long lasting effects on your body. You may also need medical tests for a short time after you stop using this medication.

If you have hepatitis B you may develop liver symptoms after you stop taking this medication, even months after stopping. Your doctor may want to check your liver function for several months after you stop using Arzerra.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What other drugs will affect Arzerra?

Other drugs may interact with ofatumumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Highlights for Arzerra

Arzerra is used to treat chronic lymphocytic leukemia.

Arzerra is available in an intravenous (IV) solution. It’s only given by a healthcare provider. You won’t give yourself this drug.

Arzerra is a brand name for the drug ofatumumab. It isn’t available as a generic drug.

IMPORTANT INFORMATION
  • FDA Warning See Details

  • Low blood cell counts See Details

  • Immunizations See Details

  • Infections See Details

What is ofatumumab?

This drug is a prescription drug. It’s available as an intravenous (IV) drug. It’s only given by a healthcare provider. You won’t give yourself this drug.

This drug is used as part of a combination therapy. This means you will need to take it with other drugs.

Why it's used

This drug is used to treat chronic lymphocytic leukemia (CLL). 

How it works

This drug belongs to a class of drugs called monoclonal antibodies.

More Details

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