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BESPONSA is a brand name for Inotuzumab Ozogamicin, supplied as a powder for solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: BESPONSA (inotuzumab ozogamicin for injection) is indicated for: • Monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL). 1.1 Pediatrics Pediatrics (< 18 years of age): Based on the data submitted and reviewed by Health Canada the safety…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations • For patients with circulating lymphoblasts, cytoreduction with a combination of hydroxyurea, steroids, and/or vincristine to a peripheral blast count ≤10,000/mm3 is recommended prior to the first dose. • Premedication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing (see 4 DOSAGE AND ADMINISTRATION, Dosing Considerations).
Patients should be observed during and for at least 1 hour after the end of infusion for symptoms of infusion-related reactions (see 4 DOSAGE AND ADMINISTRATION, Dosing Considerations, and 7 WARNINGS AND PRECAUTIONS, Immune, Infusion-related reactions).
• BESPONSA must be reconstituted and diluted before administration. For instructions on reconstitution and dilution of the medicinal product before administration, see 4 DOSAGE AND ADMINISTRATION, Instructions for Reconstitution, Dilution, and Administration.
2 Recommended Dose and Dosage Adjustment Administer BESPONSA intravenously by infusion over 1 hour. Do not administer BESPONSA as an intravenous push or bolus. Administer BESPONSA in 3- to 4-week cycles. For patients proceeding to HSCT, the recommended duration of treatment with BESPONSA is 2 cycles.
A third cycle should be considered for those patients who do not achieve a CR or a CRi and MRD negativity after 2 cycles (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic, Hepatotoxicity, including VOD/SOS). For patients with a CR or CRi and MRD negativity not proceeding to HSCT, a maximum of 6 cycles may be administered.
Any patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment. Table 1 shows the recommended dosing regimens. 5 mg/m2). Cycle 1 is BESPONSA® Product Monograph Page 6 of 44 Unclassified / Non classifié 3 weeks in duration, but may be extended to 4 weeks if the patient achieves a CR or a CRi, and/or to allow recovery from toxicity.
5 mg/m2) for patients who do not achieve a CR or CRi. Subsequent cycles are 4 weeks in duration. Table 1. 5 Cycle length 28 daysf Abbreviations: CR= complete remission; CRi= complete remission with incomplete hematologic recovery. a +/- 2 days (maintain minimum of 6 days between doses).
b Dose is based on the patient’s body surface area (m2). , 7-day treatment-free interval starting on Day 21). d CR is defined as <5% of blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥100 x 109/L and absolute neutrophil counts [ANC] ≥1 x 109/L) and resolution of any extramedullary disease.
). If the dose is reduced due to BESPONSA-related toxicity, the dose must not be re-escalated. Table 2 and Table 3 show the dose modification guidelines for hematologic and non-hematologic toxicities, respectively. , Days 8 and/or 15) do not need to be interrupted due to neutropenia or thrombocytopenia, but dosing interruptions within a cycle are recommended for non-hematologic toxicities.
Table 2. Dose Modifications for Hematologic Toxicities Hematologic toxicity Dose modification(s) If prior to BESPONSA treatment: ANC was ≥1 x 109/L If ANC decreases, then interrupt the next cycle of treatment until recovery of ANC to ≥1 x 109/L.
Platelet count was ≥50 x 109/La If platelet count decreases, then interrupt the next cycle of treatment until platelet count recovers to ≥50 x 109/La. ANC was <1 x 109/L and/or platelet count was <50 x 109/La If ANC and/or platelet count decreases, then interrupt the next cycle of treatment until at least one of the following occurs: - ANC and platelet count recover to at least baseline levels for the prior cycle, or - ANC recovers to ≥1 x 109/L and platelet count recovers to ≥50 x 109/La, 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 BESPONSA-related toxicity).
Abbreviation:
ANC= absolute neutrophil count. a Platelet count used for dosing should be independent of blood transfusion. Table 3. Dose Modifications for Non-hematologic Toxicities Non-hematologic toxicity Dose modification(s) VOD/SOS or other severe liver toxicity Permanently discontinue treatment (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic, Hepatotoxicity, including VOD/SOS).
5 x ULN prior to each dose unless due to Gilbert’s syndrome or hemolysis. 5 x ULN (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic, Hepatotoxicity, including VOD/SOS). Infusion-related reaction Interrupt the infusion and institute appropriate medical management.
3 Pharmacokinetics, Special Populations and Conditions). 2 Geriatrics Geriatrics (> 65 years of age): In a randomized clinical study of BESPONSA for the treatment of patients with ALL (Study 1), 30/164 (18%) patients treated with BESPONSA were ≥65 years of age.
No overall differences were observed in the safety and efficacy of BESPONSA between patients who were ˂65 and ≥65 years of age. However, increased age was associated with an increased risk of venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) after hematopoietic stem cell transplant (HSCT) (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic, Hepatotoxicity, including VOD/SOS).
2 CONTRAINDICATIONS BESPONSA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTH COMPOSITION AND PACKAGING section of the product monograph.
3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions • Post-hematopoietic stem cell transplant (HSCT) non-relapse mortality (see 7 WARNINGS AND PRECAUTIONS, General, Post HSCT non-relapse mortality) • Hepatotoxicity, including venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) which may be severe, life-threatening or fatal, has been observed in patients receiving BESPONSA (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic, Hepatotoxicity, including VOD/SOS) • Myelosuppression/cytopenias, and complications including infections and bleeding/hemorrhagic events, which may be severe, life-threatening or fatal, were reported in patients receiving BESPONSA (see 7 WARNINGS AND PRECAUTIONS, BESPONSA® Product Monograph Page 5 of 44 Unclassified / Non classifié Hematologic, Myelosuppression/cytopenias) • Tumor lysis syndrome (TLS), which may be severe, life-threatening or fatal, has been observed in patients receiving BESPONSA (see 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism, Tumor lysis syndrome).
BESPONSA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTH COMPOSITION AND PACKAGING section of the product monograph.
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e CRi is defined as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100 x 109/L and/or ANC <1 x 109/L) and resolution of any extramedullary disease.
f 7-day treatment-free interval starting on Day 21. Dose Modification Dose modification of BESPONSA may be required based on individual safety and tolerability (see 7 WARNINGS AND PRECAUTIONS). Management of some adverse drug reactions may require dosing interruptions and/or dose reductions, or permanent discontinuation of BESPONSA (see 7 WARNINGS BESPONSA® Product Monograph Page 7 of 44 Unclassified / Non classifié AND PRECAUTIONS, and 8 ADVERSE REACTIONS).
If the dose is reduced due to BESPONSA-related toxicity, the dose must not be re-escalated. Table 2 and Table 3 show the dose modification guidelines for hematologic and non-hematologic toxicities, respectively. , Days 8 and/or 15) do not need to be interrupted due to neutropenia or thrombocytopenia, but dosing interruptions within a cycle are recommended for non-hematologic toxicities.
Table 2. Dose Modifications for Hematologic Toxicities Hematologic toxicity Dose modification(s) If prior to BESPONSA treatment: ANC was ≥1 x 109/L If ANC decreases, then interrupt the next cycle of treatment until recovery of ANC to ≥1 x 109/L.
Platelet count was ≥50 x 109/La If platelet count decreases, then interrupt the next cycle of treatment until platelet count recovers to ≥50 x 109/La. ANC was <1 x 109/L and/or platelet count was <50 x 109/La If ANC and/or platelet count decreases, then interrupt the next cycle of treatment until at least one of the following occurs: - ANC and platelet count recover to at least baseline levels for the prior cycle, or - ANC recovers to ≥1 x 109/L and platelet count recovers to ≥50 x 109/La, 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 BESPONSA-related toxicity).
Abbreviation:
ANC= absolute neutrophil count. a Platelet count used for dosing should be independent of blood transfusion. Table 3. Dose Modifications for Non-hematologic Toxicities Non-hematologic toxicity Dose modification(s) VOD/SOS or other severe liver toxicity Permanently […]
Depending on the severity of the infusion- related reaction, consider discontinuation of the infusion BESPONSA® Product Monograph Page 8 of 44 Unclassified / Non classifié Table 3. Dose Modifications for Non-hematologic Toxicities Non-hematologic toxicity Dose modification(s) or administration of steroids and antihistamines.
For severe or life-threatening infusion reactions, permanently discontinue treatment (see 7 WARNINGS AND PRECAUTIONS, Immune, Infusions-related reaction). Non-hematologic toxicity ≥Grade 2a Interrupt treatment until recovery to Grade 1 or pre- treatment grade levels prior to each dose.
Abbreviations:
ALT= alanine aminotransferase; AST= aspartate aminotransferase; VOD/SOS= venoocclusive liver disease/sinusoidal obstruction syndrome; ULN= upper limit of normal. 0 Table 4 shows the dose modification guidelines depending on the duration of dosing interruptions due to toxicity.
Table 4 Dose Modifications Depending on Duration of Dosing Interruption Due to Toxicity Duration of dosing interruption due to toxicity Dose modification(s) <7 days (within a cycle) Interrupt next dose (maintain a minimum of 6 days between doses).
≥7 days Omit 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.
Special Populations and Conditions Pediatrics (< 18 years of age):
The safety and efficacy of BESPONSA in the pediatric population have not been established; therefore, Health Canada has not authorized an indication for pediatric use. (see 1 INDICATIONS, Pediatrics). Currently available data are described in section 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions but no recommendation on a posology can be made.
Geriatrics (> 65 years of age):
Based on a population pharmacokinetic analysis of pooled data in 765 patients with relapsed or refractory ALL [n=234] and relapsed or refractory non-Hodgkin lymphoma (NHL) [n=531] (range: 18-92 years; n=314 ≥65 years), the effect of age on clearance and volume of distribution was not significant.
No adjustment to the starting dose is required based on age (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions, Geriatrics).
Hepatic Impairment:
No formal studies of inotuzumab ozogamicin in patients with hepatic BESPONSA® Product Monograph Page 9 of 44 Unclassified / Non classifié impairment have been conducted. 5 × ULN (see 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions, Hepatic insufficiency).
5 × ULN prior to dosing. 5 × ULN prior to each dose unless due to Gilbert’s syndrome or hemolysis. 5 × ULN (see Table 5; 10 CLINICAL PHARMACOLOGY, Special Populations and Conditions).
Renal Impairment:
No formal studies of inotuzumab ozogamicin in patients […]
1 Dosing Considerations • For patients with circulating lymphoblasts, cytoreduction with a combination of hydroxyurea, steroids, and/or vincristine to a peripheral blast count ≤10,000/mm3 is recommended prior to the first dose. • Premedication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing (see 4 DOSAGE AND ADMINISTRATION, Dosing Considerations).
Patients should be observed during and for at least 1 hour after the end of infusion for symptoms of infusion-related reactions (see 4 DOSAGE AND ADMINISTRATION, Dosing Considerations, and 7 WARNINGS AND PRECAUTIONS, Immune, Infusion-related reactions).
• BESPONSA must be reconstituted and diluted before administration. For instructions on reconstitution and dilution of the medicinal product before administration, see 4 DOSAGE AND ADMINISTRATION, Instructions for Reconstitution, Dilution, and Administration.
2 Recommended Dose and Dosage Adjustment Administer BESPONSA intravenously by infusion over 1 hour. Do not administer BESPONSA as an intravenous push or bolus. Administer BESPONSA in 3- to 4-week cycles. For patients proceeding to HSCT, the recommended duration of treatment with BESPONSA is 2 cycles.
A third cycle should be considered for those patients who do not achieve a CR or a CRi and MRD negativity after 2 cycles (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic, Hepatotoxicity, including VOD/SOS). For patients with a CR or CRi and MRD negativity not proceeding to HSCT, a maximum of 6 cycles may be administered.
Any patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment. Table 1 shows the recommended dosing regimens. 5 mg/m2). Cycle 1 is BESPONSA® Product Monograph Page 6 of 44 Unclassified / Non classifié 3 weeks in duration, but may be extended to 4 weeks if the patient achieves a CR or a CRi, and/or to allow recovery from toxicity.
5 mg/m2) for patients who do not achieve a CR or CRi. Subsequent cycles are 4 weeks in duration. Table 1. 5 Cycle length 28 daysf Abbreviations: CR= complete remission; CRi= complete remission with incomplete hematologic recovery. a +/- 2 days (maintain minimum of 6 days between doses).
b Dose is based on the patient’s body surface area (m2). , 7-day treatment-free interval starting on Day 21). d CR is defined as <5% of blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥100 x 109/L and absolute neutrophil counts […]