oh-fa-TOO-moo-mab

Therapeutic Classification: anti-multiple sclerosis agents, antineoplastics

Pharmacologic Classification: monoclonal antibodies

• Chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.
• Previously untreated patients with CLL when fludarabine is considered inappropriate (in combination with chlorambucil).
• Extended treatment of patients who are in complete or partial response after 2 lines of therapy for recurrent or progressive CLL.
• Relapsed CLL (in combination with fludarabine and cyclophosphamide).
• Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

• A monoclonal antibody that specifically binds to CD20 molecule found on the surface of B lymphocytes, resulting in B-cell lysis.

• ↓numbers of leukemic cells in CLL.
• Decreased incidence of relapses in MS.

Absorption: IV administration results in complete bioavailability. Extent of absorption following subcutaneous administration unknown.

Distribution: Unknown.

Metabolism/Excretion: Undergoes enzymatic degradation to smaller peptides.

Half-life: IV — 14 days (range: 2.3–61.5 days); Subcut — 16 days.

(plasma concentrations)

Contraindicated in:

• Acute hepatitis B infection (subcut only).

Use Cautiously in:

• History of hepatitis B infection (may reactivate)
• OB: Safety not established in pregnancy (may cause fetal B-cell depletion)
• Lactation: Safety not established in breastfeeding
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CNS: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML), headache, weakness.

CV: peripheral edema.

Derm: sweating.

GI: HEPATITIS B INFECTION OR REACTIVATION, INTESTINAL OBSTRUCTION.

Hemat: anemia, neutropenia, thrombocytopenia.

Local: injection reactions (subcut only).

MS: back pain, muscle spasm.

Misc: Infection, infusion reactions, chills, fever, tumor lysis syndrome.

Drug-Drug:

• May ↓ antibody response to and ↑ risk of adverse reactions from live-virus vaccines; may also interfere with effectiveness of inactivated vaccines.
• Immunosuppressants may ↑ risk of immunosuppression.

Refractory CLL

• IV (Adults): 300 mg initially, followed 1 wk later by 2000 mg weekly for 7 doses, followed 4 wk later by 2000 mg every 4 wk for 4 doses (total regimen is 12 doses).

Previously Untreated CLL

• IV (Adults): 300 mg initially, followed 1 wk later by 1000 mg (on Day 8; Cycle 1), followed by 1000 mg on Day 1 of subsequent 28–day cycles for a minimum of 3 cycles until best response or a maximum of 12 cycles.

Extended Treatment of CLL

• IV (Adults): 300 mg initially, followed 1 wk later by 1000 mg (on Day 8), followed by 1000 mg 7 wk later and then every 8 wk thereafter for up to a maximum of 2 years.

Relapsed CLL

• IV (Adults): 300 mg initially, followed 1 wk later by 1000 mg (on Day 8; Cycle 1), followed by 1000 mg on Day 1 of subsequent 28–day cycles for a maximum of 6 cycles.

Relapsing MS

• SC (Adults): 20 mg once weekly for 3 wk (Wk 0, 1, and 2), then 20 mg once monthly starting on Wk 4.

• Solution for IV injection: 20 mg/mL;
• Solution for subcutaneous injection (prefilled pens and syringes): 20 mg/0.4 mL;

• Monitor for infusion reactions (bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema); may occur more frequently with first 2 infusions. Administer in facilities equipped to monitor and treat infusion reactions. Institute medical management for severe infusion reactions. Interrupt infusion for infusion reactions of any severity. For Grade 4 reactions, do not resume infusion. For Grade 1, 2, or 3, if infusion reaction resolves or remains less than or equal to Grade 2, resume infusion at one-half of previous infusion rate if Grade 1 or 2, or at a rate of 12 mL/hr if Grade 3. After resuming, infusion rate may be ↑ as described under rate, as tolerated.
• Assess for new signs or symptoms suggestive of PML, an opportunistic infection of the brain caused by the JC virus, leading to death or severe disability; withhold dose and notify health care professional promptly. Monitor during therapy and for at least 6 mo following discontinuation. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of the brain is infected (mental function declines rapidly and progressively, causing dementia; speaking becomes increasingly difficult; partial blindness; difficulty walking; rarely, headaches and seizures occur). Diagnosis is usually made via gadolinium-enhanced MRI and CSF analysis. Risk of PML increases with the number of infusions. Withhold ofatumumab at first sign of PML.
• Screen all patients for hepatitis B virus (HBV) infection before starting therapy. Monitor carriers of HBV for clinical and laboratory signs during and for at least 12 mo following discontinuation of therapy. Discontinue ofatumumab in patients who develop viral hepatitis or reactivation of viral hepatitis and institute appropriate treatment.
• Monitor patient for tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hypophosphatemia). Risks are higher in patients with greater tumor burden and rapidly proliferating tumors; may be fatal. Correct electrolyte abnormalities, hydrate patient, administer antihyperuricemic agents, monitor renal function and fluid balance, and administer supportive care, including dialysis, as needed.

• Perform testing for quantitative serum immunoglobulins before starting therapy. May require immunology consult if serum immunoglobulins are low.Monitor CBC and platelet counts regularly during therapy and ↑ frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. May cause prolonged (1 wk) severe neutropenia and thrombocytopenia.

• Administer all immunizations according to immunization guidelines at least 4 wks before starting of Kesimpta for live or live-attenuated vaccines and at least 2 wks for inactivated vaccines. Vaccines are not recommended until B-cell repletion.
• SC: Remove from refrigerator and allow to reach room temperature for 15–30 min before use. Solution is clear to slightly opalescent, and colorless to slightly brownish-yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter. Administer first injection under the guidance of a health care professional. Inject in the abdomen, thigh, or outer upper arm. Do not give injection into moles, scars, stretch marks or areas where the skin is tender, bruised, red, scaly or hard. Pens and syringes are for one-time use; discard after use.
• Refractory CLL: Premedicate 30 min-2 hr prior to each dose with acetaminophen PO 1000 mg, PO or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg or equivalent), and IV corticosteroid (prednisolone 100 mg or equivalent). Do not reduce corticosteroid dose for Doses 1, 2, and 9. Corticosteroid dose may be reduced for doses 3–8 and 10–12. Doses 3–8: Gradually reduce corticosteroid dose with each infusion if a reaction Grade 3 did not occur with preceding does. Doses 10–12: Administer prednisolone 50–100 mg or equivalent if a reaction Grade 3 did not occur with dose 9.
• Previously Untreated CLL, Relapsed CLL, or Extended Treatment in CLL: Premedicate 30 min-2 hr prior to each dose with acetaminophen PO 1000 mg, PO or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg or equivalent), and IV corticosteroid (prednisolone 50 mg or equivalent). If Grade 3 infusion-reaction did not occur during first 2 infusions, dose of corticosteroid may be reduced or omitted for subsequent infusions.

IV Administration:

• Intermittent Infusion:
  Diluent: Dilute all doses in 1000 mL of 0.9% NaCl in a polyolefin bag. For 300 mg dose: Withdraw and discard 15 mL from 0.9% NaCl bag. Withdraw 5 mL from each of 3 ofatumumab vials and add to 0.9% NaCl bag. For 2000 mg dose: Withdraw and discard 100 mL from 0.9% NaCl bag. Withdraw 5 mL from each of 20 ofatumumab vials and add to 0.9% NaCl bag. Do not shake; mix diluted solution by gentle inversion. Solution is clear and colorless, and may contain a small amount of visible translucent-to-white, amorphous particles; do not administer if discolored, cloudy, or if foreign matter is present Refrigerate solution, do not freeze; protect vials from light. Start infusion within 12 hr of preparation; discard after 24 hr.
• Refractory CLL: Rate: Administer through in-line filter supplied with medication using an infusion pump and PVC infusion set. Flush IV line with 0.9% NaCl before and after each dose. Do not administer as a IV push or bolus. Initiate infusion for Dose 1:300 mg at 3.6 mg/hr (12 mL/hr), Dose 2:2000 mg at 24 mg/hr (12 mL/hr), Doses 3–12:2000 mg at 50 mg/hr (25 mL/hr). Rate for Doses 1 and 2 may be ↑ every 30 min to 12, 25, 50, 100, and 200 mL/hr if no infusional toxicity occurs. Rate for Doses 3–12 may be ↑ every 30 min to 50, 100, 200, and 400 mL/hr if no infusional toxicity occurs. Do not exceed infusion rates.
• Previously Untreated CLL, Relapsed CLL, and Extended Treatment in CLL: Rate: Administer through in-line filter supplied with medication using an infusion pump and PVC infusion set. Flush IV line with 0.9% NaCl before and after each dose. Do not administer as a IV push or bolus. Initiate infusion for Cycle 1, Day 1:300 mg at 3.6 mg/hr (12 mL/hr), Cycle 1, Day 8 and Cycles 2 through 12:1000 mg at 25 mg/hr (25 mL/hr). Initiate infusion at rate of 12 mg/hr if a Grade 3 infusion-related adverse event experienced during previous infusion. Rate for Cycle 1, Day 1:may be ↑ every 30 min to 12, 25, 50, 100, 200, 300, and 400 mg/hr if no infusional toxicity occurs. Rate for Cycle 1, Day 8 and Cycles 2 through 12:may be ↑ every 30 min to 25, 50, 100, 200, 300, and 400 mg/hr if no infusional toxicity occurs. Do not exceed infusion rates. Infusion duration — Cycle 1, Day 1:5.2 hrs, Cycle 1, Day 8 :4.4 hrs, and Cycles 2 through 12:4.2–4.4 hrs. If infusion reaction resolves or remains Grade 2, resume infusion based on initial Grade of infusion reaction. Grade 1 or 2: Infuse at 1/2 of previous infusion rate. Grade 3 or 4: Infuse at 12 mL/hour. May increase as above. If severity of infusion reaction does not resolve to Grade 2 despite intervention or if anaphylactic reaction occurs, permanently discontinue ofatumumab.
• Y-Site Incompatibility: Do not mix with or infuse with other products.

• Explain the purpose of ofatumumab to patient and caregiver. Instruct patient taking Kesimpta in correct preparation, injection technique, and equipment disposal. Administer missed doses as soon as remembered, then administer subsequent doses at recommended intervals.
• Advise patient to avoid live viral vaccines during therapy.
• Advise patient to notify health care professional immediately if signs and symptoms of infusion reactions (fever, chills, rash, breathing problems) occur within 24 hr of infusion or if bleeding, PML (progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes). bruising, petechiae, pallor, worsening weakness, fatigue, cough, infection, confusion, dizziness, loss of balance, difficulty talking or walking, vision problems, yellow discoloration of skin or eyes, new or worsening abdominal pain or nausea occur.
• Rep: Advise females of reproductive potential to use effective contraception during and for 6 mo after last dose and to notify health care professional if breastfeeding. May cause fetal B-cell depletion. Avoid administering live vaccines to neonates and infants exposed to ofatumumab in utero until B-cell recovery occurs.
• Emphasize the need for periodic blood count monitoring.

• ↓numbers of leukemic cells in CLL.
• Decreased incidence of relapses in MS.

Arzerra, Kesimpta

NDC Code^*

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0669- ARZERRA
    • 0078-0669-13- 3 VIAL, SINGLE-USE in 1 CARTON (0078-0669-13) > 5 mL in 1 VIAL, SINGLE-USE (0078-0669-61)

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0690- ARZERRA
    • 0078-0690-61- 50 mL in 1 VIAL, SINGLE-USE (0078-0690-61)