in-oh-TOOZ-ue-mab oh-zoe-ga-MYE-sin

Therapeutic Classification: antineoplastics

Pharmacologic Classification: drug-antibody conjugates

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

• The antibody portion (inotuzumab) attaches to the CD22 antigen on the surface of tumor cells. A cytotoxic agent (N-acetyl-gamma-calicheamicin) is linked to the antibody portion. Binding of the antibody-drug conjugate to the CD22 antigen allows internalization of the complex into the leukemic cells. Once internalized, the N-acetyl-gamma-calicheamicin is released and binds to DNA resulting in breaks in double strand DNA and cell death.

• Achievement of complete remission.

Absorption: IV administration results in complete bioavailability.

Distribution: Distributed to tissues.

Protein Binding: 97%.

Metabolism/Excretion: N-acetyl-gamma-calicheamicin primarily metabolized via non-enzymatic reduction.

Half-life: 12.3 days.

(plasma concentrations)

Contraindicated in:

• OB: May cause fetal harm in pregnancy
• Lactation: Avoid breast feeding.

Use Cautiously in:

• Hematopoietic stem cell transplant (HSCT) after inotuzumab ozogamicin treatment, use of HSCT conditioning regimens containing two alkylating agents, last total bilirubin level the upper limit of normal prior to HSCT, hepatic impairment, prior HSCT, increased age, later salvage lines, and greater number of inotuzumab ozogamicin cycles (↑ risk of hepatic veno-occlusive disease [VOD])
• History of QT interval prolongation, receiving QT-interval prolonging medications, or electrolyte abnormalities
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established.

CNS: headache.

CV: QTc interval prolongation.

Endo: hyperuricemia.

GI: hepatotoxicity(including hepatic VOD), abdominal pain, constipation, ↓ appetite, diarrhea, ↑liver enzymes, nausea, stomatitis, vomiting, ascites, ↑ amylase, ↑ lipase.

GU: ↓fertility.

Hemat: hemorrhage, neutropenia, thrombocytopenia, anemia, lymphopenia.

Misc: DEATH (POST-HSCT), INFECTION, fatigue, fever, infusion-related reactions, tumor lysis syndrome.

Drug-Drug:

• QT interval prolonging medications may ↑ risk of QT interval prolongation.

• IV (Adults): Cycle 1 (duration = 3–4 wk) — 0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8, and 0.5 mg/m² on Day 15. Subsequent cycles for patients who achieve complete remission or complete remission with incomplete hematologic recovery (duration = 4 wk) — 0.5 mg/m² on Day 1, 0.5 mg/m² on Day 8, and 0.5 mg/m² on Day 15. Subsequent cycles for patients who do not achieve complete remission or complete remission with incomplete hematologic recovery (duration = 4 wk) — 0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8, and 0.5 mg/m² on Day 15; patients who do not achieve a complete remission or complete remission with incomplete hematologic recovery within a total of 3 cycles should discontinue treatment.

• Lyophilized powder for injection (must be reconstituted and diluted further): 0.9 mg/vial;

• Monitor for signs and symptoms of veno-occlusive disease [VOC] (↑ total bilirubin, hepatomegaly [may be painful], rapid weight gain, ascites) during therapy. Permanently discontinue inotuzumab ozogamicin if VOC occurs.
• Monitor for signs and symptoms of infection (fever, chills, sore throat, painful urination) post-HSCT.
• Monitor closely for signs and symptoms of infusion related reactions (fever, chills, rash, breathing problems) during and for at least 1 hr after the end of infusion. Interrupt infusion and institute symptom management. If reaction severe, consider discontinuation of infusion or administration of steroids and antihistamines. If interruption of cycle <7 days (within a cycle), interrupt next dose to maintain a minimum of 6 days between doses. If interruption 7 days, omit next dose within the cycle. If interruption 14 days, once recovery achieved, ↓ total dose by 25% for subsequent cycle. If further dose modification required,↓ number of doses to 2 per cycle for subsequent cycles. If 25% decrease in total dose followed by a decrease to 2 doses per cycle is not tolerated, permanently discontinue treatment. For severe or life-threatening infusion reactions, permanently discontinue inotuzumab ozogamicin.
• Monitor ECG and electrolytes prior to start of infusion, after initiation of any drug that may prolong QTc, and periodically clinically indicated.

• Verify pregnancy status before starting therapy.
  • Monitor liver tests (ALT, AST, total bilirubin, alkaline phosphatase) prior to and following each dose. If total bilirubin >1.5 × upper limit of normal (ULN) and AST/ALT >2.5 × ULN, hold dose until recovery of total bilirubin to 1.5 × ULN and AST/ALT to 2.5 × ULN prior to each dose unless due to Gilbert’s syndrome or hemolysis. If interruption of cycle <7 days (within a cycle), interrupt next dose to maintain a minimum of 6 days between doses. If interruption 7 days, omit next dose within the cycle. If interruption 14 days, once recovery achieved, ↓ total dose by 25% for subsequent cycle. If further dose modification required,↓ number of doses to 2 per cycle for subsequent cycles. If 25% decrease in total dose followed by a decrease to 2 doses per cycle is not tolerated, permanently discontinue treatment. Permanently discontinue inotuzumab ozogamicin if total bilirubin does not recover to 1.5 × ULN or AST/ALT does not recover to 2.5 × ULN.
  • Monitor CBC and platelet count prior to each dose. If pre-treatment ANC 1 × 10⁹ /L, and ANC ↓, interrupt next cycle until recovery of ANC to 1 × 10^{9 /L. If low ANC persists >28 days and is suspected to be related to inotuzumab ozogamicin, discontinue inotuzumab ozogamicin. If pre-treatment platelet count 50 x 109/L, and platelet count ↓, hold dose until platelet count recovers to 50 x 109/L. If low platelet count persists for >28 days and is suspected to be related to inotuzumab ozogamicin, permanently discontinue inotuzumab ozogamicin. If pre-treatment ANC <1 × 109/L and/or platelet count <50 × 109/L, and ANC or platelet count ↓, hold dose until at least one of the following occurs — ANC and platelet counts recover to at least baseline levels for prior cycle, or — ANC recovers to 1 × 109 /L and platelet count recovers to 50 × 109/L, or — Stable or improved disease (based on most recent bone marrow assessment) and ANC and platelet count ↓ is considered to be due to underlying disease (not inotuzumab ozogamicin-related toxicity).}
  • May cause increased serum lipase and amylase, and hyperuricemia.

• High Alert:Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
• Premedicate with a corticosteroid, antipyretic, and antihistamine prior to dosing. Observe patient during and for at least 1 hr after end of infusion for symptoms of infusion related reactions.

IV Administration:

• Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
• Reconstitute each vial with 4 mL sterile water for injection for a concentration of 0.25 mg/mL with 3.6 mL in vial. Gently swirl to dissolve; do not shake. Solution is clear to opalescent, colorless to slightly yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter. Use reconstituted solution immediately or within 4 hr if refrigerated. Do not freeze; protect from light.
  Diluent: Withdraw dose from vials and add to 0.9% NaCl for a volume of 50 mL. Recommended infusion containers include polyvinyl chloride (PVC) (di(2-ethylhexyl)phthalate [DEHP]- or non-DEHP-containing), polyolefin (polypropylene and/or polyethylene), or ethylene vinyl acetate (EVA). Invert gently to mix; do not shake. Use solution immediately. Stable for up to 4 hrs at room temperature or 3 hrs if refrigerated. Do not freeze; protect from light.
• Rate: Allow refrigerated solution to reach room temperature over 1 hr before infusing. Infuse over 1 hr at a rate of 50 mL/hr through infusion line of Infusion lines made of PVC (DEHP- or non-DEHP-containing), polyolefin (polypropylene and/or polyethylene), or polybutadiene. Infuse within 8 hrs of reconstitution. Protect solution from light.
• Y-Site Incompatibility: Do not administer with other medication in same line.

• Explain purpose of medication to patient.
• Inform patient of potential for adverse reactions including increased risk of post-HSCT non-relapse mortality.
• Instruct patient to notify health care professional immediately if signs and symptoms of hepatotoxicity (rapid weight gain, potentially painful abdominal swelling), infection, bleeding (fatigue, dyspnea, blood in stools or urine), or infusion related reactions (fever, chills, rash, breathing problems) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep: Advise patient that this medication may have teratogenic effects. Advise females to use effective contraception during and for at least 8 mo after therapy is concluded and to avoid breast feeding for at least 2 mo after last dose. Advise males with female partner of reproductive potential to use effective contraception during and for at least 5 mo after last dose. Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding. Inform female and male patients that inotuzumab ozogamicin may impair fertility.

• Achievement of complete remission.

Besponsa

• Deficient fluid volume (Adverse Reactions).

NDC Code^*

• 0008- Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
  • 0008-0100- Besponsa
    • 0008-0100-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (0008-0100-01) > 4 mL in 1 VIAL, SINGLE-DOSE