Ofatumumab

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.

Ofatumumab may be found in some form under the following brand names:

• Arzerra

No drug interactions have been determined by the manufacturer. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Ofatumumab falls into category C. There are no well-controlled studies that have been done in pregnant women. Ofatumumab should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Ofatumumab is a monoclonal antibody that affects the actions of the body's immune system. Monoclonal antibodies are made to target and destroy only certain cells in the body. This may help to protect healthy cells from damage.

Ofatumumab is used to treat chronic lymphocytic leukemia (CLL). In some patients, ofatumumab is given with another medicine called chlorambucil.

Ofatumumab is sometimes given after other medications have been tried without success.

Ofatumumab may also be used for purposes not listed in this medication guide.

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.

Contraindications

• No known contraindications.1

Warnings/Precautions

Warnings

Reactivation of HBV infection (including fulminant hepatitis, hepatic failure, and death) reported in patients receiving anti-CD20 monoclonal antibodies, including ofatumumab.1 15 16 17 18

Reactivation reported in patients with the following serologic markers: hepatitis B surface antigen-positive [HBsAg-positive]; HBsAg-negative and hepatitis B core antibody-positive [anti-HBc-positive]; or HBsAg-negative, anti-HBc-positive, and hepatitis B surface antibody-positive [anti-HBs-positive].1 15

FDA's review of 109 reports of fatal HBV-related acute liver injury in patients receiving ofatumumab or rituximab revealed highly variable onset of HBV reactivation (from 63 days after initiation of therapy to 12 months after last dose) and recent or concomitant use of other immunosuppressive agents in all 32 patients with documented (by seroconversion or serum HBV DNA) HBV reactivation.15 Longer intervals to HBV reactivation (up to 24 months after completion of rituximab therapy) also reported.16 22

Screen all patients for HBV infection prior to initiation of ofatumumab therapy.1 15 20 21 Consult hepatitis expert regarding monitoring and antiviral prophylaxis for patients with evidence of HBV infection (HBsAg-positive with any antibody status or HBsAg-negative and anti-HBc-positive).1 15 Monitor patients with evidence of current or prior HBV infection for clinical or laboratory manifestations of hepatitis or HBV reactivation during therapy and for several months thereafter.1 15

If HBV reactivation occurs, discontinue ofatumumab and any concomitant chemotherapy immediately and initiate appropriate treatment (e.g., antiviral therapy).1 15 Discontinue concomitant chemotherapy until control or resolution of HBV infection is achieved.15 Consult expert in managing HBV infection regarding resumption of ofatumumab once control of HBV reactivation has been achieved.1 Safety of resuming ofatumumab not known.1 15

PML (which may be fatal) reported.1 12 Consider PML in any patient with new or worsening neurologic manifestations.1 If PML is suspected, discontinue ofatumumab and initiate diagnostic evaluation (e.g., consultation with neurologist) as clinically indicated.1

Other Warnings and Precautions

Risk of serious infusion-related reactions (e.g., bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, angioedema). 1 Generally occur more frequently during the first 2 infusions than during subsequent infusions of the drug.1 5

In a clinical trial in patients with moderate to severe COPD, grade 3 bronchospasm occurred in 2 of 5 patients during ofatumumab infusions.1

Premedication (acetaminophen, antihistamine, and corticosteroid) recommended prior to each infusion.1 (See Premedication under Dosage and Administration.)

Monitor patients closely during infusions of the drug for manifestations of infusion-related reactions.1

Interrupt the infusion if an infusion-related reaction of any severity occurs.1 (See Rate of Administration under Dosage and Administration.)

Provide appropriate treatment and supportive care for severe reactions (e.g., angina, other manifestations of myocardial ischemia).1

Tumor lysis syndrome reported.1

Employ appropriate measures (e.g., aggressive IV hydration, antihyperuricemic therapy, correction of blood chemistries, monitoring of renal function) as clinically indicated.1

Risk of severe, prolonged (lasting ≥1 week) neutropenia; risk of thrombocytopenia.1

Monitor CBCs and platelet counts at regular intervals; more frequent monitoring recommended in patients with grade 3 or 4 cytopenia.1

Fatal HBV infection reported in patients not previously infected with the virus.1 Monitor for clinical and laboratory evidence of hepatitis.1

Small bowel obstruction reported.1 12 Perform diagnostic evaluation if symptoms are suggestive of obstruction (e.g., abdominal pain, repeated vomiting).1

Avoid immunization with live virus vaccines in patients who have recently received ofatumumab (safety not established).1

Ability of patients who have received ofatumumab therapy to generate a primary or anamnestic humoral response to any vaccine has not been studied.1

Monitor CBCs and platelet counts at regular intervals; more frequent monitoring recommended in patients with grade 3 or 4 cytopenia.1

Bacterial, viral, or fungal infections reported with ofatumumab therapy in 70% of patients with relapsed or refractory B-CLL; 29% of patients receiving the drug had grade 3 or 4 infections and 12% had fatal infections.1 12

Potential for immunogenicity with the use of therapeutic proteins such as ofatumumab.1 13 In one study, tests for antibodies to ofatumumab either yielded negative results (in 33 and 39% of patients tested after the eighth and twelfth doses, respectively) or were inconclusive (because of assay interference by high concentrations of circulating ofatumumab).1 13

Specific Populations

Category C.1

Not known whether ofatumumab is distributed into milk.1 Human IgG distributes into milk, although systemic absorption of these maternal antibodies in breast-fed infants does not appear to be substantial.1 Use ofatumumab with caution, since effects of local GI and limited systemic exposure to the drug are unknown.1

Safety and efficacy not established in children.1

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Safety and efficacy not established.1

Safety and efficacy not established.1

Common Adverse Effects

Neutropenia,1 5 pneumonia,1 pyrexia,1 cough,1 diarrhea,1 anemia,1 5 fatigue,1 dyspnea,1 rash,1 nausea,1 bronchitis,1 upper respiratory infection.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak.
• Upset stomach.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Note: Premedicate with acetaminophen, an antihistamine, and a corticosteroid 30 to 120 minutes prior to treatment (see Premedication below).

Chronic lymphocytic leukemia (CLL), previously untreated: IV: Cycle 1 (cycle is 28 days): 300 mg on day 1, followed by 1,000 mg on day 8; Subsequent cycles: 1,000 mg on day 1 every 28 days; continue for at least 3 cycles until best response or a maximum of 12 cycles (in combination with chlorambucil) (Hillmen 2015)

Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 50 mg or equivalent). Full dose corticosteroid is recommended for the first 2 infusions; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for subsequent infusions.

CLL, relapsed: IV: Cycle 1 (cycle is 28 days): 300 mg on day 1, followed by 1,000 mg on day 8; Subsequent cycles: 1,000 mg on day 1 every 28 days; continue for a maximum of 6 cycles (in combination with fludarabine and cyclophosphamide) (Robak 2017)

Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 50 mg or equivalent). Full dose corticosteroid is recommended for the first 2 infusions; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for subsequent infusions.

CLL, refractory: IV: Initial dose: 300 mg on day 1, followed 1 week later by 2,000 mg once weekly for 7 doses (doses 2 to 8), followed 4 weeks later by 2,000 mg once every 4 weeks for 4 doses (doses 9 to 12; for a total of 12 doses) (Wierda 2010)

Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 100 mg or equivalent). Full dose corticosteroid is recommended for doses 1, 2, and 9; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for doses 3 to 8; may administer reduced corticosteroid dose (ranging from half to full dose) with doses 10 to 12 if ≥ grade 3 reaction did not occur with dose 9.

CLL, extended treatment: IV: 300 mg on day 1, followed by 1,000 mg on day 8, followed by 1,000 mg 7 weeks later and then every 8 weeks for up to a maximum of 2 years (van Oers 2015)

Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 50 mg or equivalent). Full dose corticosteroid is recommended for the first 2 infusions; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for subsequent infusions.

Prepare all doses in 1,000 mL NS. Begin infusion within 12 hours of preparation.

300 mg dose: Withdraw 15 mL from a 1,000 mL NS bag. Add contents of 3 ofatumumab 100 mg vials to NS bag. Gently invert to mix; do not shake.

1,000 mg dose: Withdraw 50 mL from a 1,000 mL NS bag. Add contents of 1 ofatumumab 1,000 mg vial. Gently invert to mix; do not shake.

2,000 mg dose: Withdraw 100 mL from a 1,000 mL NS bag. Add contents of 2 ofatumumab 1,000 mg vials to NS bag. Gently invert to mix; do not shake.

Do not administer IV push, IV bolus, or as a subcutaneous injection. Premedicate with acetaminophen, an antihistamine, and a corticosteroid 30 to 120 minutes prior to administration (see Dosing). Infuse in an environment equipped to monitor for and manage infusion reactions. Administer with infusion pump and administration set. Do not exceed infusion rates below. Do not mix with or infuse with other medications. Flush line before and after infusion with NS. Begin infusion within 12 hours of preparation. Interrupt infusion for any severity of infusion reaction; if the reaction resolves or remains at ≤ grade 2, may resume infusion (see Dosage Adjustment for Toxicity).

Previously untreated chronic lymphocytic leukemia (CLL), relapsed CLL, and extended treatment of CLL:

Initial 300 mg dose: Initiate infusion at 12 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 25 mL/hour for 30 minutes, if tolerated, increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for 30 minutes, if tolerated increase to 300 mL/hour for 30 minutes, if tolerated, increase to 400 mL/hour for remainder of infusion. Median duration of infusion: 4.8 to 5.2 hours.

Subsequent 1,000 mg infusions (if no reaction to previous infusion): Initiate infusion at 25 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for 30 minutes, if tolerated, increase to 400 mL/hour for remainder of infusion. Median duration of infusion: 4.2 to 4.4 hours.

Refractory CLL:

Doses 1 and 2: Initiate infusion at 12 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 25 mL/hour for 30 minutes, if tolerated, increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for remainder of infusion. Median duration of infusion: 6.8 hours.

Doses 3 to 12: Initiate infusion at 25 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for 30 minutes, if tolerated, increase to 400 mL/hour for remainder of infusion. Median duration of infusion: 4.2 to 4.4 hours.

No formal studies of this drug in patients with renal impairment have been performed.

No formal studies of this drug in patients with renal impairment have been performed. No dose adjustment is recommended for mild to moderate renal impairment (creatinine clearance greater than 30 mL/min).