Version May 2024
Hepatotoxicity, including fatal and life-threatening veno-occlusive disease (VOD) occurred in patients with relapsed or refractory acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin. The risk of VOD was greater in patients who underwent hematopoietic stem cell transplant (HSCT) after inotuzumab ozogamicin treatment; use of HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin level ≥ upper limit of normal (ULN) before HSCT were significantly associated with an increased risk of VOD.
Other risk factors for VOD in patients treated with inotuzumab ozogamicin included ongoing or prior liver disease, prior HSCT, increased age, later salvage lines, and a greater number of inotuzumab ozogamicin treatment cycles.
Elevation of liver tests may require dosing interruption, dose reduction, or permanent discontinuation of inotuzumab ozogamicin. Permanently discontinue treatment if VOD occurs. If severe VOD occurs, treat according to standard medical practice.
There was higher post-HSCT non-relapse mortality rate in patients receiving inotuzumab ozogamicin, resulting in a higher Day 100 post-HSCT mortality rate.
Note: Administer prophylactic anti-infectives and employ surveillance testing during and after treatment. Premedication is recommended prior to inotuzumab ozogamicin infusion.
Acute lymphoblastic leukemia, B-cell precursor, relapsed/refractory: Premedication is recommended prior to dosing. Prior to the first dose, cytoreduction to a peripheral blast count of ≤10,000/mm3 with a combination of hydroxyurea, steroids, and/or vincristine is recommended for patients with circulating lymphoblasts.
Cycle 1: IV: 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15 of a 21-day treatment cycle (total dose/cycle 1: 1.8 mg/m2); treatment cycle may be extended to 4 weeks if complete remission (CR) is achieved, or CR with incomplete hematologic recovery (CRi) and/or to allow for recovery from toxicity (Ref).
Subsequent cycles:
Patients who achieve CR or CRi: IV: 0.5 mg/m2 on days 1, 8 and 15 of a 28-day treatment cycle (total dose/cycle: 1.5 mg/m2) (Ref).
Patients who do NOT achieve CR or CRi: IV: 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15 of a 28-day treatment cycle (total dose/cycle: 1.8 mg/m2); if CR or CRi is not achieved within 3 cycles, discontinue treatment (Ref).
Treatment duration: The recommended duration of treatment is 2 cycles for patients proceeding to hematopoietic cell transplant (HCT); may consider a third cycle in patients who do not achieve CR or CRi and minimal residual disease (MRD) negativity after 2 cycles. For patients not proceeding to HSCT, may continue treatment for a maximum of up to 6 cycles.
Premedication: A corticosteroid, an antipyretic, and an antihistamine are recommended prior to inotuzumab ozogamicin infusion (observe for symptoms of infusion reaction during and for at least 1 hour after the end of the infusion).
Note: Doses on days 8 and 15 may be varied by ±2 days (maintain a minimum of 6 days between doses). CR is defined as <5% blasts in bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥100,000/mm3 and ANC ≥1,000/mm3) and resolution of any extramedullary disease. CRi is defined as <5% blasts in bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100,000/mm3 and/or ANC <1,000/mm3) and resolution of any extramedullary disease.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 15 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, pharmacokinetics in this patient population are similar to those in patients with normal kidney function. Dosage adjustment is not necessary (Ref).
End-stage renal disease (ESRD) with or without hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, no need for dosage adjustment is expected (Ref).
Hepatic impairment prior to treatment initiation:
Total bilirubin ≤1.5 times ULN and AST/ALT ≤2.5 times ULN: No initial dosage adjustment necessary.
Total bilirubin >1.5 times ULN and/or AST/ALT >2.5 times ULN: There are no dosage adjustments provided in the manufacturer's labeling; however, no need for dosage adjustment is expected (Ref).
Hepatotoxicity during treatment:
Sinusoidal obstruction syndrome (also known as veno-occlusive disease [VOD]) or other severe liver toxicity: Discontinue permanently.
Total bilirubin >1.5 times ULN and AST/ALT >2.5 times ULN: Interrupt treatment 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 syndrome or hemolysis. Permanently discontinue treatment if total bilirubin does not recover to ≤1.5 times ULN or AST/ALT does not recover to ≤2.5 times ULN. Refer to Dosing: Adjustment for Toxicity for dose modifications depending on duration of treatment interruption.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2 (Ref). Note: According to the prescribing information, if a dose is reduced due to toxicity, do not re-escalate the dose.
Note: According to the prescribing information, if a dose is reduced due to toxicity, do not re-escalate the dose.
Doses within a treatment cycle (eg, day 8 and/or day 15 doses) do not need to be interrupted due to neutropenia or thrombocytopenia; however, dosing interruptions within a cycle are recommended for nonhematologic toxicities.
|
Criteria |
Inotuzumab ozogamicin dose modification(s) |
|---|---|
|
a Platelet count used for dosage modification should be independent of transfusion. | |
|
If prior to inotuzumab ozogamicin treatment ANC was ≥1,000/mm3 |
If ANC decreases, then interrupt the next cycle of treatment until recovery of ANC to ≥1,000/mm3. Discontinue inotuzumab ozogamicin if low ANC persists for >28 days and is suspected to be related to inotuzumab ozogamicin. |
|
If prior to inotuzumab ozogamicin treatment platelet count was ≥50,000/mm3 a |
If platelet count decreases, then interrupt the next cycle of treatment until platelet count recovers to ≥50,000/mm3. Discontinue inotuzumab ozogamicin if low platelet count persists for >28 days and is suspected to be related to inotuzumab ozogamicin. |
|
If prior to inotuzumab ozogamicin treatment ANC was <1,000/mm3 and/or platelet count was <50,000/mm3 a |
If ANC or platelet count decreases, then interrupt the next cycle of treatment until at least one of the following occurs: ANC and platelet counts recover to at least baseline levels for the prior cycle, or ANC recovers to ≥1,000/mm3 and platelet count recovers to ≥50,000/mm3, or stable or improved disease (based on most recent bone marrow assessment) and the ANC and platelet count decrease is considered to be due to the underlying disease (not considered to be inotuzumab ozogamicin-related toxicity). |
|
Duration of dose interruption due to toxicity |
Inotuzumab ozogamicin dose modification(s) |
|---|---|
|
<7 days (within a cycle) |
Interrupt the next dose (maintain a minimum of 6 days between doses). |
|
≥7 days |
Omit the next dose within the cycle. |
|
≥14 days |
Once adequate recovery is achieved, decrease the total dose by 25% for the subsequent cycle. If further dose modification is required, then reduce the number of doses to 2 per cycle for subsequent cycles. If a 25% decrease in the total dose followed by a decrease to 2 doses per cycle is not tolerated, then permanently discontinue treatment. |
|
>28 days |
Consider permanent discontinuation of treatment. |
|
Nonhematologic toxicity |
Inotuzumab ozogamicin dose modification(s) |
|---|---|
|
Bleeding/Hemorrhage |
May require dosing interruption, dose reduction, or permanent discontinuation. |
|
Hepatotoxicity |
See "Dosage: Hepatic Function Impairment". |
|
Infection (severe) |
May require dosing interruption, dose reduction, or permanent discontinuation. |
|
Infusion-related reaction |
Interrupt the infusion and institute appropriate medical management. Depending on the severity of the infusion related reaction, consider discontinuation of the infusion or administration of corticosteroids and antihistamines. For severe or life-threatening infusion reactions, permanently discontinue treatment. |
|
Other nonhematologic toxicity ≥ grade 2 |
Interrupt treatment until recovery to grade 1 or pretreatment grade levels prior to each dose. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Fatigue (35%), headache (28%), chills (11%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (21% to 67%), hyperuricemia (4% to 16%)
Gastrointestinal: Increased serum lipase (9% to 32%), nausea (31%), abdominal pain (23%), diarrhea (17%), constipation (16%), vomiting (15%), increased serum amylase (5% to 15%), stomatitis (13%), decreased appetite (12%)
Hematologic & oncologic: Thrombocytopenia (51%; grade 3: 14%; grade 4: 28%), neutropenia (49%; grade 3: 20% to 49%; grade 4: 27%), anemia (36%; grade ≥3%: 24%), leukopenia (35%; grade ≥3: 33%), hemorrhage (grade ≥3: 5% to 33%), febrile neutropenia (26%; grade ≥3: 26%), lymphocytopenia (18%; grade ≥3: 16%)
Hepatic: Increased serum AST (71%), increased serum alkaline phosphatase (13% to 57%), increased serum ALT (49%), increased serum transaminases (26%), hepatic veno-occlusive disease (≤23%), hyperbilirubinemia (21%), hepatotoxicity (14%)
Infection: Infection (48%)
Respiratory: Epistaxis (15%)
Miscellaneous: Fever (32%)
1% to 10%:
Cardiovascular: Prolonged QT interval on ECG (1%)
Gastrointestinal: Abdominal distention (6%)
Hematologic & oncologic: Bone marrow failure (2%; includes bone marrow failure, febrile bone marrow aplasia), tumor lysis syndrome (2%)
Hepatic: Ascites (4%)
Immunologic: Antibody development (anti-inotuzumab antibodies: 3%)
Miscellaneous: Infusion related reaction (2%; grade 2: 2%; includes hypersensitivity)
Frequency not defined: Infection: Bacterial infection, fungal infection, viral infection
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to inotuzumab or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Hematologic toxicity, including thrombocytopenia and neutropenia commonly occur (including grades 3 and 4). Neutropenic fever occurred in over one-fourth of patients; may be life-threatening. For patients who were in complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the end of treatment, the time to platelet recovery (>50,000/mm3) was >45 days after the last dose in <10% of patients. Complications associated with myelosuppression (including infections and bleeding/hemorrhagic events) have been observed.
• Hemorrhage: Hemorrhagic events associated with thrombocytopenia have been reported, including grades 3 or 4 hemorrhagic events and one grade 5 (fatal) intra-abdominal hemorrhage. The most common hemorrhagic event was epistaxis.
• Hepatotoxicity: Hepatotoxicity, including severe, life-threatening, and sometimes fatal sinusoidal obstructions syndrome (formerly called veno-occlusive disease [VOD]) has occurred in patients with relapsed or refractory acute lymphoblastic leukemia who received inotuzumab ozogamicin. The risk of VOD was greater in patients who received a hematopoietic cell transplant (HCT) following inotuzumab ozogamicin treatment. The use of HCT conditioning regimens containing 2 alkylating agents (eg, busulfan in combination with other alkylating agents) and a total bilirubin level ≥ ULN before HCT were significantly associated with increasing the risk of VOD. Other risk factors for VOD associated with inotuzumab ozogamicin included ongoing or prior liver disease, prior HCT, increased age, later salvage lines, and a higher number of inotuzumab ozogamicin treatment cycles. Patients with a history of VOD or who have serious ongoing hepatic liver disease (eg, cirrhosis, idiopathic noncirrhotic portal hypertension [including nodular regenerative hyperplasia], active hepatitis) are at an increased risk for worsening of liver disease, including developing VOD, following inotuzumab ozogamicin therapy. VOD was reported up to 56 days after the last dose during treatment or during follow-up without an intervening HCT. For patients receiving HCT after inotuzumab ozogamicin, the median time to onset of VOD was 15 days (range: 3 to 57 days). Utilize standard medical management for severe VOD. Other hepatotoxicity events have been reported, including grades 3 and 4 AST, ALT, and total bilirubin elevations.
• Hypersensitivity: Hypersensitivity reactions have been reported.
• Infections: Infections, including serious infections (some life-threatening or fatal), were reported in nearly half of patients treated with inotuzumab ozogamicin. Fatal infections, including pneumonia, neutropenic sepsis, sepsis, septic shock, and pseudomonal sepsis, have been reported; bacterial, viral, and fungal infections occurred. Administer prophylactic antimicrobial agents as appropriate.
• Infusion reactions: Grade 2 infusion related reactions were reported with inotuzumab ozogamicin administration in a small percentage of patients. Infusion reactions (eg, fever, chills, rash, dyspnea) usually occurred in cycle 1 shortly after the end of the infusion and resolved spontaneously or with medical management. Premedications are recommended.
• QT prolongation: Increases in the corrected QT interval of ≥60 msec from baseline were observed in a small number of patients (including grade 2 prolongation in some patients), although none had QTcF values greater than 500 msec. There were no ≥ grade 3 QT prolongations or cases of torsades de pointes reported. Use inotuzumab ozogamicin with caution in patients with a history of (or predisposition for) QTc prolongation, patients taking drugs known to prolong the QT interval, and/or in patients with electrolyte abnormalities.
Disease related concerns:
• Hematopoietic stem cell transplant: A higher post-HCT non-relapse mortality rate was observed in patients who received inotuzumab ozogamicin, resulting in a higher Day 100 post-HCT mortality rate. The most common causes of post-HCT non-relapse mortality included VOD and/or infection. Among patients with ongoing VOD, multiorgan failure or infection resulting in fatality occurred.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Besponsa: 0.9 mg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Besponsa Intravenous)
0.9 mg (per each): $26,682.59
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Besponsa: 0.9 mg (1 ea) [contains polysorbate 80]
Available through specialty pharmacy distributors. Information and a distributor list is available from the manufacturer at 1-877-744-5675 or at https://besponsa.pfizerpro.com/how-to-order.
IV: Infuse over 1 hour (at a rate of 50 mL/hour). If refrigerated, allow to reach room temperature for ~1 hour prior to administration. Infuse at room temperature and protect from light during infusion. Infusion sets made of PVC (DEHP-or non-DEHP-containing), polyolefin (polypropylene and/or polyethylene), or polybutadiene are recommended for administration. An inline filter is not required during administration; however, if the diluted solution is filtered, polyethersulfone (PES)-, polyvinylidene fluoride (PVDF)-, or hydrophilic polysulfone (HPS)-based filters are recommended (do not use filters made of nylon or mixed cellulose ester). Do not mix or administer with other medications.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute lymphoblastic leukemia, relapsed/refractory: Treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults.
Inotuzumab ozogamicin may be confused with gemtuzumab ozogamicin, ibritumomab
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Dabrafenib: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fluorouracil Products: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Gadobenate Dimeglumine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Halofantrine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Lofexidine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Midostaurin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Piperaquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Piperaquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Probucol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Probucol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Verify pregnancy status prior to therapy. Patients who could become pregnant should use effective contraception during therapy and for at least 8 months after the last dose. Effective contraception should also be used for at least 5 months after the last dose when treating patients with partners who could become pregnant.
Based on the mechanism of action and information from animal reproduction studies, in utero exposure to inotuzumab ozogamicin may cause fetal harm.
It is not known if inotuzumab ozogamicin is present in breast milk. Due to the potential for serious adverse reactions in the nursing infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 2 months after the last dose.
CBC (prior to each dose), LFTs including ALT, AST, total bilirubin, and alkaline phosphatase (prior to and following each dose); for patients who proceed to hematopoietic cell transplant (HCT), monitor liver function tests closely during the first month post-HCT, then less frequently thereafter, according to standard medical practice; electrolytes (prior to treatment initiation, after initiation of any drug known to prolong QTc, and periodically as clinically indicated during treatment). Verify pregnancy status prior to treatment (in patients who could become pregnant). Obtain ECG (prior to treatment initiation, after initiation of any drug known to prolong QTc, and periodically as clinically indicated during treatment).
Monitor closely for signs and symptoms of veno-occlusive disease (VOD) (eg, total bilirubin elevations, hepatomegaly with or without pain, rapid weight gain, ascites); monitor closely for toxicities post-HCT (including infection and VOD). Monitor for signs/symptoms of effects of myelosuppression (bleeding, hemorrhage, infection) during treatment. Monitor for hypersensitivity; monitor closely during the infusion and for at least 1 hour after the end of the infusion for the potential infusion reactions. Monitor for signs and symptoms of tumor lysis syndrome (TLS), including renal function, electrolytes, and uric acid frequently during the risk period of TLS.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Inotuzumab ozogamicin is a humanized CD22-directed monoclonal antibody-drug conjugate which is composed of the IgG4 kappa antibody inotuzumab (which is specific for human CD22), a calicheamicin component (a cytotoxic agent that causes double-stranded DNA breaks), and an acid-cleavable linker that covalently binds the calicheamicin to inotuzumab. After the antibody-drug conjugate binds to CD22, the CD22-conjugate complex is internalized, and releases calicheamicin. Calicheamicin binds to the minor groove of DNA to induce double strand cleavage and subsequent cell cycle arrest and apoptosis (Kantarjian 2016).
Note: Body surface area was found to significantly affect disposition.
Distribution: ~12 L
Protein binding: Calicheamicin: ~97% bound to human plasma proteins
Metabolism: Calicheamicin: Primarily via nonenzymatic reduction
Half-life, elimination: 12.3 days
Excretion: Clearance (steady state): 0.0333 L/hour
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
