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BESPONSA (inotuzumab ozogamicin) for injection

2017-08-27 14:17:36 来源: 作者: 【大中小】浏览:508次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use BESPONSA™ safely and effectively. See full prescribing information for BESPONSA.

BESPONSA (inotuzumab ozogamicin) for injection, for intravenous use
Initial U.S. Approval: 2017
WARNING: HEPATOTOXICITY, INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE (VOD) (ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME and INCREASED RISK OF POST- HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) NON-RELAPSE MORTALITY
See full prescribing information for complete boxed warning.

Hepatotoxicity, including fatal and life-threatening VOD occurred in patients who received BESPONSA. (5.1)
A higher post-HSCT non-relapse mortality rate occurred in patients receiving BESPONSA (5.2)

INDICATIONS AND USAGE

BESPONSA is a CD22-directed antibody-drug conjugate (ADC) indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). (1)
DOSAGE AND ADMINISTRATION

Pre-medicate with a corticosteroid, antipyretic, and antihistamine prior to all infusions. (2.2)

Dosing regimens for Cycle 1 and subsequent cycles, depending on the response to treatment, are shown below. See full prescribing information for dosing details. (2)

	Day 1	Day 8	Day 15
* For patients who achieve a CR or a CRi, and/or to allow for recovery from toxicity, the cycle length may be extended up to 28 days (i.e., 7-day treatment-free interval starting on Day 21).
Dosing regimen for Cycle 1
All patients:
Dose	0.8 mg/m2	0.5 mg/m2	0.5 mg/m2
Cycle length	21 days*
Dosing regimen for subsequent cycles depending on response to treatment
Patients who have achieved a CR or CRi:
Dose	0.5 mg/m2	0.5 mg/m2	0.5 mg/m2
Cycle length	28 days
Patients who have not achieved a CR or CRi:
Dose	0.8 mg/m2	0.5 mg/m2	0.5 mg/m2
Cycle length	28 days

See full prescribing information for instructions on reconstitution of lyophilized powder, and preparation and administration of reconstituted drug. (2.4)

DOSAGE FORMS AND STRENGTHS

For injection: 0.9 mg lyophilized powder in a single-dose vial for reconstitution and further dilution. (3)
CONTRAINDICATIONS

None (4)
WARNINGS AND PRECAUTIONS

Myelosuppression: Monitor complete blood counts; for signs and symptoms of infection; bleeding/hemorrhage; or other effects of myelosuppression during treatment; manage appropriately. (5.3)
Infusion related reactions: Monitor for infusion related reactions during and for at least 1 hour after infusion ends. (5.4)
QT interval prolongation: Obtain electrocardiograms (ECGs) and electrolytes at baseline and monitor during treatment. Monitor more frequently when using concomitant mediations known to prolong QT interval. (5.5)
Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.6)

ADVERSE REACTIONS

The most common (≥ 20%) adverse reactions are thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyltransferase increased, and hyperbilirubinemia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed. (8.2)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 8/2017

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: HEPATOTOXICITY, INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE (VOD) (ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME and INCREASED RISK OF POST-HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) NON-RELAPSE MORTALITY

1. INDICATIONS AND USAGE

2. DOSAGE AND ADMINISTRATION

3. DOSAGE FORMS AND STRENGTHS

4. CONTRAINDICATIONS

5. WARNINGS AND PRECAUTIONS

6. ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Immunogenicity

7. DRUG INTERACTIONS

8. USE IN SPECIFIC POPULATIONS

11. DESCRIPTION

12. CLINICAL PHARMACOLOGY

13. NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14. CLINICAL STUDIES

15. REFERENCES

16. HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage and Handling

17. PATIENT COUNSELING INFORMATION

*: Sections or subsections omitted from the full prescribing information are not listed.

1. INDICATIONS AND USAGE

BESPONSA is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

2. DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Pre-medicate before each dose [see Dosage and Administration (2.2)].
For the first cycle, the recommended total dose of BESPONSA for all patients is 1.8 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Cycle 1 is 3 weeks in duration, but may be extended to 4 weeks if the patient achieves a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), and/or to allow recovery from toxicity.
For subsequent cycles:
- In patients who achieve a CR or CRi, the recommended total dose of BESPONSA is 1.5 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.5 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration.
  OR
- In patients who do not achieve a CR or CRi, the recommended total dose of BESPONSA is 1.8 mg/m2 per cycle given as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Subsequent cycles are 4 weeks in duration. Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment.
For patients proceeding to hematopoietic stem cell transplant (HSCT), the recommended duration of treatment with BESPONSA is 2 cycles. A third cycle may be considered for those patients who do not achieve CR or CRi and minimal residual disease (MRD) negativity after 2 cycles [see Warnings and Precautions (5.1)].
For patients not proceeding to HSCT, additional cycles of treatment, up to a maximum of 6 cycles, may be administered.

Table 1 shows the recommended dosing regimens.

Table 1. Dosing Regimen for Cycle 1 and Subsequent Cycles Depending on Response to Treatment
	Day 1	Day 8*	Day 15*
Abbreviations: CR=complete remission; CRi=complete remission with incomplete hematologic recovery.
* +/- 2 days (maintain minimum of 6 days between doses). † Dose is based on the patient's body surface area (m 2). ‡ For patients who achieve a CR or a CRi, and/or to allow for recovery from toxicity, the cycle length may be extended up to 28 days (i.e., 7-day treatment-free interval starting on Day 21). § CR is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥ 100 × 10 9/L and absolute neutrophil counts [ANC] ≥ 1 × 10 9/L) and resolution of any extramedullary disease. ¶ 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 × 10 9/L and/or ANC < 1 × 10 9/L) and resolution of any extramedullary disease. # 7-day treatment-free interval starting on Day 21.
Dosing regimen for Cycle 1
All patients:
Dose†	0.8 mg/m2	0.5 mg/m2	0.5 mg/m2
Cycle length	21 days‡
Dosing regimen for subsequent cycles depending on response to treatment
Patients who have achieved a CR§ or CRi¶:
Dose†	0.5 mg/m2	0.5 mg/m2	0.5 mg/m2
Cycle length	28 days#
Patients who have not achieved a CR§ or CRi¶:
Dose†	0.8 mg/m2	0.5 mg/m2	0.5 mg/m2
Cycle length	28 days#

2.2 Recommended Pre-medications and Cytoreduction

Premedication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing. Patients should be observed during and for at least 1 hour after the end of infusion for symptoms of infusion related reactions [see Warnings and Precautions (5.4)].
For patients with circulating lymphoblasts, cytoreduction with a combination of hydroxyurea, steroids, and/or vincristine to a peripheral blast count of less than or equal to 10,000/mm3 is recommended prior to the first dose.