Names and pronunciation
(ih-noh-too′-zoo-mab oh′-zoh- ga-MIH-sin) Besponsa
PDF page 701
Loading InternPractice…
Drug reference
(ih-noh-too′-zoo-mab oh′-zoh- ga-MIH-sin) Besponsa
PDF page 701
Func. class.: Antineoplastic monoclo- nal antibodies
PDF page 701
ACTION: A CD22-directed antibody- drug conjugate; CD22 is expressed on pre–B cells and mature B cells. It con- sists of a cytotoxic agent; it induces DNA breaks, resulting in cell-cycle arrest and apoptotic cell death
PDF page 701
USES: For the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia
PDF page 701
CONTRAINDICATIONS: Preg- nancy, hypersensitivity
PDF page 701
Black Box Warning: Hepatic disease, hepatotoxicity, mortality, sinusoidal obstructive disease, veno-occlusive disease Precautions: Alcoholism, bleeding, breastfeeding, contraception require- ments, diabetes mellitus, electrolyte imbalances, females, geriatric patients, infertility, male-mediated teratogenicity, neutropenia, bone marrow suppres- sion, infection, reproductive risk, thrombocytopenia, thyroid disease, QT prolongation Black Box Warning: Severe or life- threatening hepatotoxicity including veno-occlusive disease (VOD)/sinu- soidal obstruction syndrome (SOS): monitor liver function tests (LFTs), total bilirubin, alkaline phosphatase lev- els before and following each dosage change; therapy interruption, dose re- I duction, or permanent discontinuation may be necessary in those who develop LFT abnormalities. Closely monitor for VOD/SOS (hepatomegaly, rapid weight gain, and ascites). Permanently discon- tinue in those who develop VOD/SOS; in those who undergo a hematopoietic stem-cell transplant (HSCT), monitor LFTs frequently during the first month post-HSCT; then, continue to monitor LFTs but less often. Time from HSCT to onset of VOD/SOS was 15 days (range, 3 to 57 days). The risk of VOD/SOS may be greater in patients who receive an HSCT or a conditioning regimen that contains 2 alkylating agents before HSCT and in patients who have an in- creased total bilirubin level before an HSCT; other risk factors include hepatic disease (e.g., cirrhosis, nodular regen- erative hyperplasia, active hepatitis), a prior HSCT, increased age, later salvage lines, and a greater number of treat- ment cycles Black Box Warning: Mortality: those who underwent a hematopoietic stem- cell transplant (HSCT) may have a higher 100-day post-HSCT nonrelapse mortal- ity; monitor closely for post-HSCT toxicity. The most common causes of post-HSCT death were veno-occlusive disease/sinu- soidal obstruction syndrome and infec- tious complications • Pregnancy/breastfeeding: product can cause fetal harm; females of repro ductive potential should avoid becom ing pregnant during and for 8 mo after final dose; obtain pregnancy test before starting product; do not breastfeed dur ing and for at least 2 mo after last dose; men with female partners of reproduc tive potential should avoid fathering a child and use effective contraception during and for at least 5 mo after therapy
PDF pages 701, 702, 703, 704
SIDE EFFECTS CNS: Fatigue, fever, headache, migraine, chills GI: Nausea, vomiting, diarrhea, stomati- tis, constipation, anorexia, abdominal pain, hepatotoxicity HEMA: Anemia, thrombocytopenia, bleeding, hematoma, hematuria, ecchy- mosis, veno-occlusive disease MISC: Infection, asthenia, QT prolonga tion, tumor lysis syndrome, sinusoidal obstruction syndrome
PDF page 703
INTERACTIONS Increase: QT prolongation—other prod ucts that increase QT prolongation Drug/Lab Test Increase: LFTs
PDF page 703
DOSAGE AND ROUTES Relapsed or refractory B-cell precursor ALL • Adult: IV 0.8 mg/m2 day 1 and 0.5 mg/m2 days 8 and 15 (cycle 1). Length of cycle 1 is 21 days, may increase to 28 days Management of treatment-related toxicity • Do not interrupt doses within a treat ment cycle (day 8 or day 15 dose) for neutropenia or thrombocytopenia. Dosing interruptions within a cycle are recom mended for nonhematologic toxicity. If a dose reduction is necessary, do not re- escalate the dose Hematologic toxicity • Absolute neutrophil count (ANC) of ≥1 × 109 cells/L before starting ther- apy: if the ANC decreases, hold next cy cle until recovery of the ANC to 1 × 109 cells/L or greater. Discontinue therapy if low ANC lasts >28 days and is suspected to be due to inotuzumab ozogamicin • Platelet count of ≥50 × 109 cells/L before starting therapy: if platelet count decreases, hold next cycle until the plate let count recovers to 50 × 109 cells/L or greater. Discontinue therapy if low plate let count lasts >28 days and is suspected to be due to inotuzumab ozogamicin • ANC was <1 × 109 cells/L and/or platelet count was <50 × 109 cells/L before starting therapy: if the ANC or platelet count decreases, hold the next cycle until at least 1 of the following occurs: the ANC and platelet counts recover to baseline or better for the prior cycle; the ANC re covers to 1 × 109 cells/L or greater and the platelet count recovers to 50 × 109 cells/L or greater; the patient has sta ble or improved disease (based on most recent bone marrow assessment) and the ANC and platelet count de crease is considered to be due to the underlying disease and not product- related toxicity
PDF page 702
Available forms: Powder for injection 0.9 mg
PDF page 702
Administer: IV route • Visually inspect for particulate matter and discoloration before use • Follow cytotoxic handling procedures • Available as a single-dose, preserva- tive-free, 0.9-mg lyophilized powder vial • Premedication with a corticosteroid, an antipyretic agent (acetaminophen), and an antihistamine before each dose is recommended; observe patients during and for at least 1 hr after the end of the infusion for symptoms of infusion-related reactions Reconstitution • After calculating the number of vials needed, add 4 mL of Sterile Water for Injection to each vial for a final vial con- centration of 0.25 mg/mL (0.9 mg/3.6 mL); gently swirl the vial to dissolve powder; do not shake • The reconstitution solution should be clear to opalescent, colorless to slightly yellow, and free of visible for- eign matter • Storage of reconstituted vials: if not further diluted immediately, vials may be stored in the refrigerator (at 2°C-8°C or 36°F-46°F) for up to 4 hr after reconsti- tution; protect from light, do not freeze Dilution: • Add required dose/volume from the reconstituted vials to an infusion con- tainer made of polyvinyl chloride (PVC) (or non–DEHP-containing), polyolefin (polypropylene and/or polyethylene), or ethylene vinyl acetate (EVA); discard any unused portion • Add 0.9% sodium chloride injection to the infusion container for a final total volume of 50 mL; gently invert to mix, do not shake • Storage of admixture: if not infused immediately, the diluted solution may be stored at room temperature (20°C-25°C or 68°F-77°F) for up to 4 hr or refriger- ated (2°C-8°C or 36°F-46°F) for up to 3 hr; protect from light and do not freeze Intravenous (IV) Infusion: • Allow refrigerated admixtures to warm to room temperature for 1 hr before use • Give admixture (protected from light) as an IV infusion over 1 hr through an infusion line made of PVC, polyolefin (polypropylene and/or polyethylene), or polybutadiene • Complete infusion within 8 hr of re- constitution • The diluted solution does not need to be filtered; if it is filtered, use polyethersulfone (PES)-, polyvinylidene fluoride (PVDF)-, or hydrophilic polysulfone (HPS)-based filters • Do not use filters made of nylon or mixed cellulose ester (MCE) • Do not mix with or administer as an infusion with other drugs
PDF pages 702, 703
Assess: • Serious infection: some may be fatal. Monitor patients for signs and symptoms of infection; use prophylactic anti-infectives as appropriate • Severe myelosuppression/bone mar row suppression: thrombocytopenia, neutropenia; obtain a CBC before each dose; therapy interruption or permanent discontinuation may be necessary in patients who develop severe myelosuppression • QT prolongation: obtain an electrocar diogram (ECG) and monitor serum electro lytes before the start of treatment and peri odically as needed. Use with caution in a history of QT prolongation or electrolyte imbalance.
PDF page 703
Evaluate: • Therapeutic response: improving blood counts Teach patient/familiy: • To report adverse reactions immedi ately: bleeding; report diarrhea, hepatic, hematologic symptoms/toxicity, flulike symptoms • About reason for treatment, expected results • That monitoring for infusion reactions will be needed for at least 1 hr after infu- sion has ended • Pregnancy/breastfeeding: to notify provider if pregnancy is planned or sus pected; to use effective contraception dur ing treatment and for 8 mo after discon tinuing treatment; not to breastfeed during treatment or for 2 mo after final dose; that men with female partners of reproductive potential should avoid fathering a child and use effective contraception during and for at least 5 mo after therapy HIGH ALERT
PDF page 704
CLINICAL CONSIDERATIONS
PDF page 703
PHARMACOKINETICS Protein binding 97%
PDF page 703
• Adult: IV 0.8 mg/m2 day 1 and 0.5 mg/m2 days 8 and 15 (cycle 1). Length of cycle 1 is 21 days, may increase to 28 days Management of treatment-related toxicity
PDF page 702
• Do not interrupt doses within a treat ment cycle (day 8 or day 15 dose) for neutropenia or thrombocytopenia. Dosing interruptions within a cycle are recom mended for nonhematologic toxicity. If a dose reduction is necessary, do not re- escalate the dose Hematologic toxicity
PDF page 702
• Absolute neutrophil count (ANC) of ≥1 × 109 cells/L before starting ther- apy: if the ANC decreases, hold next cy cle until recovery of the ANC to 1 × 109 cells/L or greater. Discontinue therapy if low ANC lasts >28 days and is suspected to be due to inotuzumab ozogamicin
PDF page 702
• Platelet count of ≥50 × 109 cells/L before starting therapy: if platelet count decreases, hold next cycle until the plate let count recovers to 50 × 109 cells/L or greater. Discontinue therapy if low plate let count lasts >28 days and is suspected to be due to inotuzumab ozogamicin
PDF page 702
• ANC was <1 × 109 cells/L and/or platelet count was <50 × 109 cells/L before starting therapy: if the ANC or platelet count decreases, hold the next cycle until at least 1 of the following occurs: the ANC and platelet counts recover to baseline or better for the prior cycle; the ANC re covers to 1 × 109 cells/L or greater and the platelet count recovers to 50 × 109 cells/L or greater; the patient has sta ble or improved disease (based on most recent bone marrow assessment) and the ANC and platelet count de crease is considered to be due to the underlying disease and not product- related toxicity
PDF page 702