blinatumomab (Rx)

Brand and Other Names:Blincyto
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 35mcg/vial

Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

Indicated for relapsed or refractory CD19-positive B-cell precursor ALL in adults and children

Treatment course consists of up to 2 cycles for induction followed by 3 additional cycles for consolidation treatment and up to 4 additional cycles of continued therapy

Induction or consolidation cycle consists of 28 days of continuous IV infusion followed by a 14-day treatment-free interval between cycles (total 42 days)

Continued therapy consists of 28 days of continuous IV infusion followed by a 56-week treatment-free interval between cycles (total 84 days)

<45 kg (BSA-based dose)

  • Induction (Cycle 1)
    • Days 1-7: 5 mcg/m2/day continuous IV infusion (not to exceed 9 mcg/day), THEN  
    • Days 8-28: 15 mcg/m2/day (not to exceed 28 mcg/day)
    • Days 29-42: Treatment-free interval
  • Induction (Cycle 2)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion (not to exceed 28 mcg/day), THEN
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 3-5)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion (not to exceed 28 mcg/day), THEN  
    • Days 29-42: Treatment-free interval
  • Continued therapy (Cycles 6-9)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion (not to exceed 28 mcg/day), THEN  
    • Days 29-84: Treatment-free interval

≥45 kg (fixed dose)

  • Induction (Cycle 1)
    • Days 1-7: 9 mcg/day continuous IV infusion, THEN
    • Days 8-28: 28 mcg/day
    • Days 29-42: Treatment-free interval
  • Induction (Cycle 2)
    • Days 1-28: 28 mcg/day continuous IV infusion, THEN
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 3-5)
    • Days 1-28: 28 mcg/day continuous IV infusion
    • Days 29-42: Treatment-free interval
  • Continued therapy (Cycles 6-9)
    • Days 1-28: 28 mcg/day continuous IV infusion
    • Days 29-84: Treatment-free interval

Minimal Residual Disease-positive B-cell Precursor Acute Lymphoblastic Leukemia

Indicated for CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥0.1% in adults and children

Treatment course consists of 1 cycle for induction followed by up to 3 additional cycles for consolidation

Induction or consolidation cycle consists of 28 days of continuous IV infusion followed by a 14-day treatment-free interval between cycles (total 42 days)

<45 kg (BSA-based dose)

  • Induction (Cycle 1)
    • Day 1-28: 15 mcg/m2/day continuous IV infusion; not to exceed 28 mcg/day  
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 2-4)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion; not to exceed 28 mcg/day  
    • Days 29-42: Treatment-free interval

≥45 kg (fixed dose)

  • Induction (Cycle 1)
    • Days 1-28: 28 mcg/day continuous IV infusion  
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 2-4)
    • Days 1-28: 28 mcg/day continuous IV infusion  
    • Day 29-84: Treatment-free interval

Dosage Modifications

If interruption after an adverse event is ≤7 days, continue the same cycle to a total of 28 days of infusion, inclusive of days before and after the interruption in that cycle

If an interruption due to an adverse event is >7 days, start a new cycle

Cytokine release syndrome (CRS)

  • Grade 3
    • Interrupt infusion
    • <45 kg: Administer dexamethasone 5 mg/m2 (up to 8 mg) IV/PO q8hr for up to 3 days and taper thereafter over 4 days; once CRS is resolved, restart at 5 mcg/m2/day, and escalate to 15 mcg/m2/day after 7 days if no recurrence
    • ≥45 kg: Administer dexamethasone 8 mg IV/PO q8hr for up to 3 days and taper thereafter over 4 days; when CRS resolves, restart blinatumomab at 9 mcg/day, and increase to 28 mcg/day after 7 days if no recurrence
  • Grade 4
    • Permanently discontinue
    • Administer dexamethasone as instructed for Grade 3 CRS

Neurological toxicity

  • Seizure (>1 seizure): Permanently discontinue
  • Grade 3
    • Withhold until Grade ≤1 (mild) and for at least 3 days
    • <45 kg: Restart at 5 mcg/m2/day; increase to 15 mcg/m2/day after 7 days if no recurrence
    • ≥45 kg: Restart blinatumomab at 9 mcg/day, and increase to 28 mcg/day after 7 days if no recurrence
    • If reaction recurs at reduced dose or takes >7 days to resolve: Permanently discontinue
  • Grade 4
    • Permanently discontinue

Other clinically relevant adverse reactions

  • Grade 3
    • Withhold until Grade ≤1 (mild)
    • <45 kg: Restart at 5 mcg/m2/day, and increase to 15 mcg/m2/day after 7 days if no recurrence
    • ≥45 kg: Restart at 9 mcg/day, and increase to 28 mcg/day after 7 days if no recurrence
    • If reaction recurs at reduced dose or takes >14 days to resolve: Permanently discontinue
  • Grade 4
    • Permanently discontinue

Renal impairment

  • No formal pharmacokinetic studies conducted
  • CrCl <30 mL/min or on hemodialysis: No information available

Hepatic impairment

  • No formal pharmacokinetic studies conducted

Dosing Considerations

Hospitalization

  • Relapsed or refractory B-cell precursor ALL
    • First cycle: First 9 days
    • Second cycle: First 2 days
    • Subsequent cycle starts and reinitiation (eg, treatment interruption ≥4 hr): Supervision by a healthcare professional or hospitalization is recommended
  • MRD-positive B-cell precursor ALL
    • First cycle: First 3 days
    • Second cycle: First 2 days
    • Subsequent cycle starts and reinitiation (eg, treatment interruption ≥4 hr): Supervision by a healthcare professional or hospitalization is recommended

Diffuse Large B-cell Lymphoma (Orphan)

Orphan designation for treatment of diffuse large B-cell lymphoma (DLBCL)

Sponsor

  • Amgen Inc; 1 Amgen Center Drive; Thousand Oaks, California 91320

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 35mcg/vial

Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

Indicated for relapsed or refractory CD19-positive B-cell precursor ALL in adults and children

Treatment course consists of up to 2 cycles for induction followed by 3 additional cycles for consolidation treatment and up to 4 additional cycles of continued therapy

Induction or consolidation cycle consists of 28 days of continuous IV infusion followed by a 14-day treatment-free interval between cycles (total 42 days)

Continued therapy consists of 28 days of continuous IV infusion followed by a 56-week treatment-free interval between cycles (total 84 days)

<45 kg (BSA-based dose)

  • Induction (Cycle 1)
    • Days 1-7: 5 mcg/m2/day continuous IV infusion (not to exceed 9 mcg/day), THEN  
    • Days 8-28: 15 mcg/m2/day (not to exceed 28 mcg/day)
    • Days 29-42: Treatment-free interval
  • Induction (Cycle 2)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion (not to exceed 28 mcg/day), THEN
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 3-5)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion (not to exceed 28 mcg/day), THEN  
    • Days 29-42: Treatment-free interval
  • Continued therapy (Cycles 6-9)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion (not to exceed 28 mcg/day), THEN  
    • Days 29-84: Treatment-free interval

≥45 kg (fixed dose)

  • Induction (Cycle 1)
    • Days 1-7: 9 mcg/day continuous IV infusion, THEN
    • Days 8-28: 28 mcg/day
    • Days 29-42: Treatment-free interval
  • Induction (Cycle 2)
    • Days 1-28: 28 mcg/day continuous IV infusion, THEN
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 3-5)
    • Days 1-28: 28 mcg/day continuous IV infusion
    • Days 29-42: Treatment-free interval
  • Continued therapy (Cycles 6-9)
    • Days 1-28: 28 mcg/day continuous IV infusion
    • Days 29-84: Treatment-free interval

Minimal Residual Disease-positive B-cell Precursor Acute Lymphoblastic Leukemia

Indicated for CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥0.1% in adults and children

Treatment course consists of 1 cycle for induction followed by up to 3 additional cycles for consolidation

Induction or consolidation cycle consists of 28 days of continuous IV infusion followed by a 14-day treatment-free interval between cycles (total 42 days)

<45 kg (BSA-based dose)

  • Induction (Cycle 1)
    • Day 1-28: 15 mcg/m2/day continuous IV infusion; not to exceed 28 mcg/day  
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 2-4)
    • Days 1-28: 15 mcg/m2/day continuous IV infusion; not to exceed 28 mcg/day  
    • Days 29-42: Treatment-free interval

≥45 kg (fixed dose)

  • Induction (Cycle 1)
    • Days 1-28: 28 mcg/m2/day continuous IV infusion  
    • Days 29-42: Treatment-free interval
  • Consolidation (Cycles 2-4)
    • Days 1-28: 28 mcg/m2/day continuous IV infusion  
    • Day 29-84: Treatment-free interval

Dosage Modifications

If interruption after an adverse event is ≤7 days, continue the same cycle to a total of 28 days of infusion, inclusive of days before and after the interruption in that cycle

If an interruption due to an adverse event is >7 days, start a new cycle

Cytokine release syndrome (CRS)

  • Grade 3
    • Interrupt infusion
    • <45 kg: Administer dexamethasone 5 mg/m2 (up to 8 mg) IV/PO q8hr for up to 3 days and taper thereafter over 4 days; once CRS is resolved, restart at 5 mcg/m2/day, and escalate to 15 mcg/m2/day after 7 days if no recurrence
    • ≥45 kg: Administer dexamethasone 8 mg IV/PO q8hr for up to 3 days and taper thereafter over 4 days; when CRS resolves, restart blinatumomab at 9 mcg/day, and increase to 28 mcg/day after 7 days if no recurrence
  • Grade 4
    • Permanently discontinue
    • Administer dexamethasone as instructed for Grade 3 CRS

Neurological toxicity

  • Seizure (>1 seizure): Permanently discontinue
  • Grade 3
    • Withhold until Grade ≤1 (mild) and for at least 3 days
    • <45 kg: Restart at 5 mcg/m2/day; increase to 15 mcg/m2/day after 7 days if no recurrence
    • ≥45 kg: Restart blinatumomab at 9 mcg/day, and increase to 28 mcg/day after 7 days if no recurrence
    • If reaction recurs at reduced dose or takes >7 days to resolve: Permanently discontinue
  • Grade 4
    • Permanently discontinue

Other clinically relevant adverse reactions

  • Grade 3
    • Withhold until Grade ≤1 (mild)
    • <45 kg: Restart at 5 mcg/m2/day, and increase to 15 mcg/m2/day after 7 days if no recurrence
    • ≥45 kg: Restart at 9 mcg/day, and increase to 28 mcg/day after 7 days if no recurrence
    • If reaction recurs at reduced dose or takes >14 days to resolve: Permanently discontinue
  • Grade 4
    • Permanently discontinue

Renal impairment

  • No formal pharmacokinetic studies conducted
  • CrCl <30 mL/min or on hemodialysis: No information available

Hepatic impairment

  • No formal pharmacokinetic studies conducted

Dosing Considerations

Hospitalization

  • Relapsed or refractory B-cell precursor ALL
    • First cycle: First 9 days
    • Second cycle: First 2 days
    • Subsequent cycle starts and reinitiation (eg, treatment interruption ≥4 hr): Supervision by a healthcare professional or hospitalization is recommended
  • MRD-positive B-cell precursor ALL
    • First cycle: First 3 days
    • Second cycle: First 2 days
    • Subsequent cycle starts and reinitiation (eg, treatment interruption ≥4 hr): Supervision by a healthcare professional or hospitalization is recommended

Diffuse Large B-cell Lymphoma (Orphan)

Orphan designation for treatment of diffuse large B-cell lymphoma (DLBCL)

Sponsor

  • Amgen Inc; 1 Amgen Center Drive; Thousand Oaks, California 91320
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Interactions

Interaction Checker

and blinatumomab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (0)

              Serious - Use Alternative (1)

              • sirolimus

                blinatumomab increases levels of sirolimus by decreasing metabolism. Avoid or Use Alternate Drug. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              Monitor Closely (20)

              • carbamazepine

                blinatumomab increases levels of carbamazepine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • clonidine

                blinatumomab increases levels of clonidine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • cyclosporine

                blinatumomab increases levels of cyclosporine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • dichlorphenamide

                dichlorphenamide and blinatumomab both decrease serum potassium. Use Caution/Monitor.

              • disopyramide

                blinatumomab increases levels of disopyramide by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • ethosuximide

                blinatumomab increases levels of ethosuximide by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • fosphenytoin

                blinatumomab increases levels of fosphenytoin by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • ofatumumab SC

                ofatumumab SC, blinatumomab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

              • phenobarbital

                blinatumomab increases levels of phenobarbital by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • phenytoin

                blinatumomab increases levels of phenytoin by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • primidone

                blinatumomab increases levels of primidone by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • quinidine

                blinatumomab increases levels of quinidine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • quinine

                blinatumomab increases levels of quinine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • siponimod

                siponimod and blinatumomab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • tacrolimus

                blinatumomab increases levels of tacrolimus by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • theophylline

                blinatumomab increases levels of theophylline by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • trastuzumab

                trastuzumab, blinatumomab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • trastuzumab deruxtecan

                trastuzumab deruxtecan, blinatumomab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • valproic acid

                blinatumomab increases levels of valproic acid by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • warfarin

                blinatumomab increases levels of warfarin by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              Minor (0)

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                Adverse Effects

                >10%

                Pyrexia (55-91%)

                Infusion related reaction (30-77%)

                Other pathogen infections (28-39%)

                Headache (23-36%)

                Tremor (31%)

                Neutropenia (16-31%)

                Chills (15-28%)

                Febrile neutropenia (25%)

                Nausea (25%)

                Peripheral edema (25%)

                Hypokalemia (23%)

                Thrombocytopenia (10-21%)

                Tremor (20%)

                Constipation (20%)

                Diarrhea (20%)

                Bacterial infections (19%)

                Cough (13-19%)

                Insomnia (15-18%)

                Decreased immunoglobulins (18%)

                Fatigue (17%)

                Rash (12-16%)

                Dyspnea (15%)

                Abdominal pain (15%)

                Neutropenia, Grade 3 or more (15%)

                Hypertransaminasemia (9-15%)

                Dizziness (10-14%)

                Back pain (12-14%)

                Leukopenia (9-14%)

                Hypotension (14%)

                Bacterial infectious disorders (14%)

                Cytokine release syndrome (14%)

                Arrhythmia (12-14%)

                Vomiting (13%)

                Viral infections (11-13%)

                Pain in extremity (12%)

                Hypomagnesemia (12%)

                Increased ALT (12%)

                Aphasia (12%)

                Increased AST (11%)

                Bone pain (11%)

                Hyperglycemia (11%)

                Increased weight (11%)

                Chest pain (11%)

                Cytokine release syndrome (11%)

                Hypotension (11%)

                1-10%

                Fungal infections (10%)

                Arthralgias (10%)

                Decreased appetite (10%)

                Increased weight (10%)

                Encephalopathy (10%)

                Leukopenia, Grade 3 or more (9%)

                Pneumonia (9%)

                Hypertension (8%)

                Sepsis (7%)

                Hypophosphatemia (6%)

                Infusion-related reaction, Grade 3 or more (3-5%)

                Decreased immunoglobulins, Grade 3 or more (5%)

                Headache, Grade 3 or more (4%)

                Tremor, Grade 3 or more (4%)

                Encephalopathy, Grade 3 or more (4%)

                Arrhythmia, Grade 3 or more (2%)

                Rash, Grade 3 or more (1%)

                Postmarketing Reports

                Stomach pain

                Fatal pancreatitis

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                Warnings

                Black Box Warnings

                Cytokine release syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving blinatumomab; interrupt or discontinue depending on severity (see Dosage Modifications)

                Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving blinatumomab; interrupt or discontinue depending on severity (see Dosage Modifications)

                Contraindications

                Hypersensitivity to blinatumomab or any components of product formulation

                Cautions

                Cytokine release syndrome (CRS), which may be life-threatening or fatal, has been observed and may be clinically indistinguishable from infusion reactions; serious adverse events that may be associated with CRS included pyrexia, headache, nausea, asthenia, hypotension, increased ALT, increased AST, and increased total bilirubin; monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and total blood bilirubin prior to start of and during treatment (see Black Box Warnings)

                Neurological toxicities have occurred in ~65% of patients; median time to first event was within the first 2 weeks of treatment and majority of events resolved; ≥Grade 3 (severe, life-threatening, or fatal) neurological toxicities occurred in ~13% of patients and included encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders

                Serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections were observed in approximately 25% of patients, some of which were life-threatening or fatal

                Tumor lysis syndrome may be life-threatening or fatal; appropriate prophylactic measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used for prevention: may require either temporary interruption or discontinuation

                Neutropenia and febrile neutropenia, including life-threatening cases, observed; monitor WBC and absolute neutrophil counts during infusion; interrupt if prolonged neutropenia occurs

                Owing to the potential for neurologic events, including seizures, patients are at risk for loss of consciousness; advise patients to refrain from driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery during treatment

                Transient elevation of liver enzymes reported; interrupt if the transaminases rise to >5 xULN or if bilirubin rises to >3 xULN

                Leukoencephalopathy observed confirmed by cranial MRI, especially in patients with prior treatment with cranial irradiation and antileukemic chemotherapy (high dose methotrexate, IT cytarabine); clinical significance of this is unknown

                Preparation and administration errors have occurred; follow instructions for preparation (including admixing) and administration strictly to minimize medication errors

                Potential for immunogenicity (as with all therapeutic proteins)

                Safety of immunization with live viral vaccines during or following therapy not studied; vaccination with live virus vaccines not recommended for at least 2 weeks prior to start of treatment, during treatment, and until immune recovery following last cycle of blinatumomab

                Fatal pancreatitis reported in combination with dexamethasone in clinical trials and post-marketing setting; evaluate patients who develop signs and symptoms of pancreatitis; management of pancreatitis may require either temporary interruption or discontinuation of blinatumomab and dexamethasone

                Benzyl alcohol preservative may cause serious adverse reactions (eg, gasping syndrome) in pediatrics; gasping syndrome is CNS depression, metabolic acidosis, and gasping respirations; consider total benzyl alcohol metabolic load contains 7.4 mg of benzyl alcohol; minimum benzyl alcohol amount which adverse reactions occur is unknown

                Possible drug interactions

                • No formal drug interaction studies have been conducted Initiation of blinatumomab treatment causes transient release of cytokines that may suppress CYP450 enzymes
                • The highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the second cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index
                • In these patients, monitor for toxicity (eg, warfarin) or drug concentrations (eg, cyclosporine)
                • Adjust the dose of the concomitant drug as needed
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                Pregnancy & Lactation

                Pregnancy

                Based on mechanism of action, therapy may cause fetal harm when administered to pregnant woman; verify pregnancy status of females of reproductive potential prior to initiating treatment

                Due to potential for B-cell lymphocytopenia in infants following exposure to blinatumomab in-utero, monitor infant’s B lymphocytes before the initiation of live virus vaccination

                Advise females of reproductive potential to use effective contraception during treatment and for at least 48 hr after the last dose of blinatumomab

                Lactation

                There is no information regarding presence of blinatumomab in human milk, effects on breastfed infant, or effects on milk production; because many drugs are excreted in human milk and because of potential for serious adverse reactions in nursing infants from therapy, including B-cell lymphocytopenia, advise patients not to breastfeed during and for at least 48 hr after ending therapy

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells

                Activates endogenous T-cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells

                Blinatumomab mediates the formation of a synapse between the T-cell and the tumor cell, up-regulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells

                Absorption

                Steady-state achieved within a day of continuous IV infusion

                Peak plasma concentration at steady-state: 228 pg/mL (9 mcg/day); 616 pg/mL (28 mcg/day)

                Distribution

                Vd: 4.35 L

                Metabolism

                Metabolic pathway has not been characterized

                Like other protein therapeutics, it is expected to be degraded into small peptides and amino acids via catabolic pathways

                Elimination

                Half-life: 2.1 hr

                Clearance: 3.11 L/hr

                Excretion: Negligible amounts in urine (all doses)

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                Administration

                IV Incompatibility

                Any products containing with di-ethylhexylphthalate (DEHP)

                IV Preparation

                Reconstituting vial

                • Reconstitute 1 vial using 3 mL of preservative-free sterile water for injection; direct sterile water toward the side of the vial; resulting concentration per vial is 12.5 mcg/mL
                • Do not reconstitute vial with IV solution stabilizer
                • Gently swirl contents to avoid excess foaming; do not shake
                • Visually inspect reconstituted solution for particulate matter and discoloration during reconstitution and before infusion; resulting solution should be clear to slightly opalescent, colorless to slightly yellow; do not use if solution is cloudy or has precipitated

                IV admixture

                • For 24-hr or 48-hr infusion (preservative free)
                  • Refer to specific admixing instructions are provided for each dose
                  • Add 270 mL of 0.9% NaCl to an empty bag; transfer 5.5 mL IV solution stabilizer to 0.9% NaCl
                  • Transfer the required volume of reconstituted blinatumomab solution into bag containing 0.9% NaCl and IV solution stabilizer
                  • Gently mix the contents of the bag to avoid foaming
                  • Attach IV tubing to IV bag with the sterile 0.2 micron in-line filter; ensure that the IV is compatible with the infusion pump
                  • Remove air from IV bag, which is particularly important for use with an ambulatory infusion pump
                  • Prime IV tubing only with the solution in the bag containing the FINAL prepared blinatumomab solution for infusion; do not prime with 0.9% NaCl
                • For 7-day infusion (preservative containing)
                  • Specific admixing instructions are provided for each dose
                  • Add 90 mL of bacteriostatic 0.9% NaCl to an empty bag; transfer 2.2 mL IV solution stabilizer to saline solution
                  • Transfer reconstituted blinatumomab and bacteriostatic 0.9% NaCl to diluted solution
                  • Add required volume of 0.9% NaCl to IV bag to obtain a final volume of 110 mL; gently mix the contents of the bag to avoid foaming; see prescribing information for specific instructions for preparation
                  • Do not use inline filter for a 7-day bag
                  • Prime IV tubing only with the solution in the bag containing the FINAL prepared blinatumomab solution for infusion; do not prime with 0.9% NaCl

                IV Administration

                Administer as a continuous IV infusion at a constant flow rate using an infusion pump; the pump should be programmable, lockable, non-elastomeric, and have an alarm

                Do not flush infusion line or IV catheter, especially when changing infusion bags; flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof.

                When administering via a multi-lumen venous catheter, infuse blinatumomab through a dedicated lumen

                Premedication

                • Adults
                  • MRD-positive B-cell percussor ALL: Prednisone 100 mg IV or equivalent (eg, dexamethasone 16 mg) 1 hr prior to the first dose in each cycle
                  • Relapsed/refractory B-cell precursor ALL: Dexamethasone 20 mg IV 1 hr prior to the first dose of each cycle, prior to a step dose (eg, Cycle 1 Day 8), and when restarting an infusion after an interruption of ≥4 hr
                • Children and adolescents
                  • MRD-positive B-cell percussor ALL: Dexamethasone 5 mg/m2 (not to exceed 20 mg/dose) IV before the first dose in the first cycle and when restarting an infusion after an interruption of ≥4 hr in the first cycle
                  • Relapsed/refractory B-cell precursor ALL: Dexamethasone 5 mg/m2 (not to exceed 20 mg/dose) before the first dose in the first cycle, prior to a step dose (eg, Cycle 1 Day 8), and when restarting an infusion after an interruption of ≥4 hr

                For 24-hr or 48-hr infusion

                • Infuse over 24 hr or 48 hr
                • Infuse total 240 mL solution according to the instructions on the pharmacy label on the bag at one of the following constant infusion rates:
                  • Infusion rate of 10 mL/hr for a duration of 24 hr, OR
                  • Infusion rate of 5 mL/hr for a duration of 48 hr

                For 7-day infusion

                • Not recommended for patients weighing ≤22kg
                • Infusion rate of 0.6 mL/hr for a duration of 7 days
                • Administer using IV tubing that contains a sterile, nonpyrogenic, low protein-binding, 0.2 micron in-line filter
                • At the end of the infusion, any unused solution in the IV bag and IV lines should be disposed of in accordance with local requirements

                Do NOT flush line

                • Do not flush the infusion line, especially when changing infusion bags
                • Flushing when changing bags or at completion of infusion can result in excess dosage

                Storage

                Protect from light

                Unopened vial

                • Refrigerate drug and IV solution stabilizer vials in the original package at 2-8ºC (36-46ºF); do not freeze

                Reconstituted vial

                • Store at room temperature at 23-27°C (73-81°F): 4 hr
                • Refrigerate at 2-8ºC (36-46ºF) for up to 24 hr

                Prepared IV bag (preservative-free)

                • Store at room temperature at 23-27ºC (73-81ºF) up to 48 hr (includes infusion time)
                • Refrigerate at 2-8ºC (36-46ºF) for up to 8 days
                • If prepared infusion bag is not administered within the time frames and temperatures indicated, discard and do not be refrigerate again

                Prepared IV bag (with preservative)

                • Store at room temperature at 23-27ºC (73-81ºF) up to 7 days (includes infusion time)
                • Refrigerated at 2-8ºC (36-46ºF) for up to 8 days
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                Patient Handout

                Patient Education
                blinatumomab intravenous

                BLINATUMOMAB - INJECTION

                (BLIN-a-TOOM-oh-mab)

                COMMON BRAND NAME(S): Blincyto

                WARNING: Blinatumomab may cause certain serious (sometimes fatal) side effects, including cytokine release syndrome-CRS and infusion reactions. Symptoms may include fever, chills, headache, nausea, vomiting, stomach/abdominal pain, trouble breathing, skin rash, weakness, or low blood pressure. Blinatumomab can also cause serious brain, spinal cord, and nerve disorders with symptoms such as headache, trouble sleeping, seizures, confusion, loss of consciousness, difficulty with swallowing/facial movements, or speech and balance problems. Tell your doctor right away if you develop any of these symptoms.You may be given this medication in a hospital or clinic so your doctor can watch for these serious side effects and provide treatment if needed. If you have side effects, your doctor may temporarily stop or slow down your treatment with this medication. Also, your doctor may prescribe other medications before you receive blinatumomab to decrease the risk of side effects.

                USES: This medication is used to treat a certain type of cancer (acute lymphocytic leukemia-ALL). Blinatumomab belongs to a class of drugs known as monoclonal antibodies. It works by slowing or stopping the growth of cancer cells.

                HOW TO USE: See also Warning section.Read the Medication Guide provided by your pharmacist before you start using blinatumomab and each time you get a refill. If you have any questions, ask your doctor or pharmacist.The dosage and treatment schedule are based on your medical condition, weight, and response to treatment. To reduce your risk of side effects, your doctor may prescribe other medications (such as dexamethasone) before each treatment to help reduce side effects. Also, your doctor may start this medication at a low dose and gradually increase your dose.This medication is given by slow injection (infusion) into a vein as directed by your doctor. A special machine (infusion pump) is used for giving the injection, usually over 4 weeks (28 days), followed by a break (usually 2 weeks) during which you will not be given blinatumomab. After the break, your doctor will decide if you will be given another treatment cycle with this medication. In later treatment cycles, your breaks may be longer (8 weeks). Do not change the settings on the infusion pump since you might get the wrong dose. Ask your health care professional right away if you have any questions about the infusion pump.

                SIDE EFFECTS: See also Warning section.Nausea, heartburn, constipation, shaking (tremor), swelling ankles/feet/hands, or dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.People using this medication may have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.Blinatumomab sometimes causes side effects due to the rapid destruction of cancer cells (tumor lysis syndrome). To lower your risk, your doctor may add a medication and tell you to drink plenty of fluids. Tell your doctor right away if you have symptoms such as: low back/side pain (flank pain), signs of kidney problems (such as painful urination, pink/bloody urine, change in the amount of urine), muscle spasms/weakness.This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as fever, chills, persistent sore throat, cough).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Before using blinatumomab, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding/blood problems, brain/nerve disorders, current or returning infections, seizures.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Blinatumomab can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using blinatumomab. Blinatumomab may harm an unborn baby. Ask about reliable forms of birth control while using this medication and for 2 days after stopping treatment. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

                OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: Laboratory and/or medical tests (such as complete blood count, liver function) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

                MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.

                STORAGE: Store in the refrigerator. Do not freeze. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

                MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

                Information last revised September 2020. Copyright(c) 2021 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.