Drug information of Ofatumumab

Ofatumumab is a monoclonal antibody which binds specifically the extracellular (large and small) loops of the CD20 molecule (which is expressed on normal B lymphocytes and in B-cell CLL) resulting in potent complement-dependent cell lysis and antibody-dependent cell-mediated toxicity in cells that overexpress CD20.

Distribution

Vdss: 6.1 L (following repeated infusions)

Half-Life Elimination

17.6 days (following repeated infusions)

Labeled Indications

Chronic lymphocytic leukemia, previously untreated: Treatment of previously untreated chronic lymphocytic leukemia (CLL) (in combination with chlorambucil) when fludarabine-based therapy is considered inappropriate

Chronic lymphocytic leukemia, relapsed: Treatment of relapsed CLL (in combination with fludarabine and cyclophosphamide).

Chronic lymphocytic leukemia, refractory: Treatment of CLL refractory to fludarabine and alemtuzumab

Chronic lymphocytic leukemia, extended treatment: Extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL

Adult

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)

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)

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)

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 .

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to ofatumumab or any component of the formulation; presence or history of progressive multifocal leukoencephalopathy.

Warning

Intravenous route (Solution)

Hepatitis B Virus (HBV) reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab, 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 ofatumumab.

Side effects requiring immediate medical attention

Along with its needed effects, ofatumumab may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking ofatumumab:

More common

• Black, tarry stools
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• body aches or pain
• chest pain
• chills
• confusion
• cough or hoarseness
• cough producing mucus
• difficult or labored breathing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• ear congestion
• facial swelling
• fainting
• fast heartbeat
• feeling of warmth
• headache
• hives or welts, itching, or skin rash
• increased sweating
• lightheadedness
• loss of voice
• lower back or side pain
• nasal congestion
• nausea or vomiting
• painful blisters on the trunk of the body
• painful or difficult urination
• pale skin
• rapid weight gain
• rapid, shallow breathing
• redness of the face, neck, arms, and occasionally, upper chest
• runny nose
• sneezing
• sore throat
• tightness in the chest
• tingling of the hands or feet
• troubled breathing
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• weakness

Less common

• Fast, pounding, or irregular heartbeat or pulse
• nervousness
• pounding in the ears
• slow heartbeat

Incidence not known

• Blistering, peeling, or loosening of the skin
• dark urine
• diarrhea
• fluid-filled skin blisters
• joint or muscle pain
• light-colored stools
• no blood pressure or pulse
• red skin lesions, often with a purple center
• red, irritated eyes
• sensitivity to the sun
• skin thinness
• stopping of heart
• unconsciousness
• yellow eyes or skin

Side effects not requiring immediate medical attention

Some side effects of ofatumumab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Back pain
• muscle aches
• redness of the skin
• trouble sleeping

Less common

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• muscle spasms
• pain or tenderness around the eyes and cheekbones

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.

Ofatumumab 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 ofatumumab 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 ofatumumab and for up to several months after you stop using it. This has resulted in liver failure or death in some people using ofatumumab. Your doctor will perform blood tests to make sure you do not have conditions that may cause you to develop hepatitis B.

Using ofatumumab 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 ofatumumab.

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.

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

Ofatumumab 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 ofatumumab.

You will be given other IV or oral (by mouth) medications to prevent certain side effects of ofatumumab. 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. Ofatumumab can cause hepatitis B to come back or get worse. You will need frequent blood tests to check your liver function.

Ofatumumab 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 ofatumumab.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Solutions diluted in NS for infusion must be started within 12 hours of preparation (may store at 2°C to 8°C [36°F to 46°F] if not used immediately); discard any remaining solution 24 hours after preparation.

Benefit should outweigh risk.

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned

Comments:
-This drug may cause fetal B-cell depletion based on findings from animal studies and the mechanism of action of the drug. Live vaccines should not be administered to neonates and infants exposed to this drug in utero until B-cell recovery occurs.