inotuzumab ozogamicin

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

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 (ULN) 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: Children 1 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

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

GU: ↓fertility

Hemat: anemia, hemorrhage, lymphopenia, neutropenia, thrombocytopenia

Metab: hyperuricemia

Neuro: headache

Misc: fatigue, fever, death (post-HSCT), INFECTION, infusion-related reactions, tumor lysis syndrome

Interactions ⬆ ⬇

Drug-drug:

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

Route/Dosage ⬆ ⬇

IV (Adults and Children ≥1 yr): 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.

Availability ⬆ ⬇

Lyophilized powder for injection: 0.9 mg/vial

Assessment ⬆ ⬇

Monitor for signs and symptoms of VOD (↑ total bilirubin, hepatomegaly [may be painful], rapid weight gain, ascites) during therapy. Permanently discontinue inotuzumab ozogamicin if VOD 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 ≥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% ↓ in total dose followed by a ↓ 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 QT interval, and periodically clinically indicated.

Lab Test Considerations:

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 times ULN and AST/ALT >2.5 times ULN, hold dose until recovery of total bilirubin to ≤1.5 times ULN and AST/ALT to ≤2.5 times 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% ↓ in total dose followed by a ↓ to 2 doses per cycle is not tolerated, permanently discontinue treatment. Permanently discontinue inotuzumab ozogamicin if total bilirubin does not recover to ≤1.5 times ULN or AST/ALT does not recover to ≤2.5 times ULN.
- Monitor CBC and platelet count prior to each dose. If pretreatment 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 pretreatment 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 pretreatment 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 ↑ serum lipase and amylase, and hyperuricemia.

Implementation ⬆ ⬇

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 ≥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.
Reconstitution: 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. For doses 0.5 mg, add dose to 0.9% NaCl in a bag for a volume of 50 mL. For doses 0.5 mg, add dose to 0.9% NaCl in a syringe for a volume of 2–50 mL. Invert gently to mix; do not shake. Use solution immediately. Stable for up to 6 hr at room temperature or refrigerated. Administer diluted solution within 8 hr of reconstitution. Do not freeze; protect from light.
Rate: Allow refrigerated solution to reach room temperature over 1 hr before infusing. Infuse over 1 hr.
Y-Site Incompatibility: Do not administer with other medication in same line.

Patient/Family Teaching ⬆ ⬇

Explain purpose of medication to patient.
Inform patient of potential for adverse reactions including ↑ risk of post-HSCT nonrelapse 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: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 8 mo after therapy is concluded and to avoid breastfeeding for 2 mo after last dose. Advise males with female partner of reproductive potential to use effective contraception during and for 5 mo after last dose. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform female and male patients that inotuzumab ozogamicin may impair fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇