blinatumomab

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blinatumomab

(bli-ni-too-moe-mab),

Blincyto

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: temporary class
Pregnancy Category: C

Indications

Treatment of Philadelphia chromosome-negative relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Action

Acts as a T-cell engager, binding to and activating T-cells binding them to tumor cells resulting in facilitated lysis of malignant cells.

Therapeutic effects

Depletion of B-cells, including malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailibility.
Distribution: Unknown.
Metabolism and Excretion: Catabolized into small peptides and amino acids.
Half-life: 2.11 hr.

Time/action profile (depletion of B-cells)

ROUTEONSETPEAKDURATION
IVrapidunknownpersists during treatment free interval

Contraindications/Precautions

Contraindicated in: Hypersensitivity; CCr <30 ml/min; Lactation: discontinue blinatumomab or discontinue breastfeeding.
Use Cautiously in: Geriatric: Increased risk of neurologic toxicity; Obstetric: Use during pregnancy only if maternal benefit justifies risk to the fetus; Pediatric: limited experience, safe use not established.

Adverse Reactions/Side Effects

Central nervous system

  • seizures (life-threatening)
  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)
  • aphasia
  • cognitive disorder
  • confusion
  • leukoencephalopathy
  • weakness

Respiratory

  • cough (most frequent)
  • dyspnea (most frequent)

Cardiovascular

  • chest pain (most frequent)
  • hypotension (most frequent)
  • peripheral edema (most frequent)
  • hypertension
  • tachycardia

Gastrointestinal

  • abdominal pain (most frequent)
  • ↓ appetite (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • vomiting (most frequent)
  • ↑ liver enzymes

Dermatologic

  • rash (most frequent)

Endocrinologic

  • hyperglycemia (most frequent)

Fluid and Electrolyte

  • hypokalemia (most frequent)
  • hypomagnesemia (most frequent)
  • hypophosphatemia

Hematologic

  • neutropenia
  • anemia (most frequent)
  • ↓ albumin
  • ↓ immunoglobulins
  • thrombocytopenia
  • leukocytosis
  • lymphopenia

Musculoskeletal

  • arthralgia (most frequent)
  • back pain (most frequent)
  • bone pain (most frequent)
  • extremity pain (most frequent)

Neurologic

  • neurologic toxicity
  • tremor (most frequent)

Miscellaneous

  • cytokine release syndrome (life-threatening)
  • febrile neutropenia/infections 
  • hypersensitivity reactions (life-threatening)
  • tumor lysis syndrome (life-threatening)
  • chills (most frequent)
  • fever (most frequent)
  • infusion reactions

Interactions

Drug-Drug interaction

May suppress activity of CYP450 drug-metabolizing enzymes (especially first 9 days of first cycle and first two days of second cycle), careful monitoring of drugs that are substrates of CYP450, including cyclosporine and wafarin, is recommended.

Route/Dosage

Intravenous (Adults ≥45 kg) Cycle 1—9 mcg/day as a continuous infusion for days 1–7, followed by 28 mcg/day as a continuous infusion for days 8–28, followed by a two week treatment-free interval. Subsequent cycles—28 mcg/day for days 1–28, followed by a two week treatment-free interval. Treatment course is up to two cycles for induction followed by three additional cycles (total of five cycles).

Availability

Lyophilized powder for injection (requires reconstitution): 35 mcg/vial (IV solution stabilizer provided with package)

Nursing implications

Nursing assessment

  • Monitor for signs and symptoms of cytokine release syndrome (pyrexia, fever, headache, nausea, asthenia, hypotension, ↑ AST, ↑ ALT, ↑ bilirubin) during infusion. May be similar to infusion reactions. If symptoms are Grade 3 withhold blinatumomab until resolved, then restart at 9 mcg/day. Escalate to 28 mcg/day after 7 days if toxicity does not recur. If Grade 4 symptoms occur, discontinue blinatumomab permanently.
  • Monitor for signs and symptoms of neurological toxicity (encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion, disorientation, loss of balance and coordination) during therapy. Discontinue blinatumomab permanently if more than 1 seizure occurs. If Grade 3 symptoms occur, withhold blinatumomab until no more than Grade 1 (mild) and for at least 3 days, then restart blinatumomab at 9 mcg/day. Escalate dose to 28 mcg/day after 7 days if toxicity does not recur. If toxicity occurred at 9 mcg/day or takes >7 days to resolve, discontinue blinatumomab permanently. If Grade 4 symptoms occur, discontinue blinatumomab permanently.
  • Assess for signs and symptoms of infection (fever, chills, sepsis, pneumonia, bacteremia, opportunistic infections, catheter site infections) during therapy. Treat with anti-infectives as needed.
  • Monitor for signs and symptoms of tumor lysis syndrome (abdominal pain and distension, dysuria, oliguria, flank pain, hematuria, anorexia, vomiting, cramps, seizures, spasms, altered consciousness) during therapy. May use prophylactic nontoxic cytoreduction and on-treatment hydration. May require temporary interruption or discontinuation.
  • Lab Test Considerations: Monitor CBC periodically during therapy. May cause neutropenia. Interrupt therapy if neutropenia is prolonged.
    • Monitor ALT, AST, gamma-glutamyl transferase (GGT), and total serum bilirubin prior to starting and during therapy. If AST and ALT increase to ≥5 times the upper limit of normal or if bilirubin rises to >3 times the upper limit of normal interrupt therapy.
    • May cause hypokalemia, hypomagnesemia, hyperglycemia, and hypophosphatemia.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Patient must be hospitalized for first 9 days of first cycle and first 2 days of second cycle. For other cycles, supervision by healthcare professional is recommended.
    • Premedicate with dexamethasone 20 mg IV 1 hr prior to first dose of each cycle or when restarting infusion after interruption of 4 or more hr.
    • If an interruption due to an adverse reaction is <7 days, continue same cycle to a total of 28 days inclusive of days before and after interruption. If interruption >7 days, start a new cycle.
    • If questions occur regarding reconstitution and preparation, call 1-800-AMGEN or 1-800-772-6436.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers (see ).
  • Continuous Infusion: Do not flush line, especially when changing bags or at completion of infusion; may result in excess or overdose. Use a pre-filled 250 mL 0.9% NaCl polyolefin, PVC non-di-ethylhexylphalate (non-DEHP), or ethyl vinyl acetate (EVA) bag.
    • Stabilizer is used to coat prefilled IV bag; add IV stabilizer to bag, do not use for reconstitution.
    • Entire volume of admixed blinatumomab will be more than 240 mL volume administered to patient to account for priming and ensure patient received full dose. Remove air from infusion bag. Add or remove 0.9% NaCl from bag if needed to adjust volume to 265 to 275 mL.
    • Using 10 mL syringe, transfer 5.5 mL of IV solution stabilizer to IV bag. Gently mix; avoid foaming. Discard remaining stabilizer.
    • Reconstitute blinatumomab, using 3 mL preservative-free Sterile Water for Injection/vial for a concentration of 12.5 mg/mL. Direct solution toward side of vial; gently swirl to avoid foaming. Do not shake. Solution should be clear to opalescent; do not infuse solutions that are discolored or contain a precipitate. Vials are stable at room temperature for 4 hr or 24 hr if refrigerated. For 9 mcg/day infused over 24 hr at a rate of 10 mL/hr, transfer 0.83 mL of reconstituted solution into IV bag. For 9 mcg/day infused over 48 hr at a rate of 5 mL/hr, transfer 2.6 mL of reconstituted solution into IV bag. For 28 mcg/day infused over 24 hr at a rate of 10 mL/hr, transfer 2.6 mL of reconstituted solution into IV bag. For 28 mcg/day infused over 48 hr at a rate of 5 mL/hr,transfer 5.2 mL of reconstituted solution (2.7 mL from one vial and 2.5 mL from a second vial) into IV bag. Diluted solution is stable for 48 hr at room temperature or for 8 days if refrigerated.
  • Rate: Infuse via programmable, lockable, non-elastomeric infusion pump with an alarm. Infuse 240 mL over 24 or 48 hr based on pharmacy label, at a rate of 10 mL/hr for 24 hr or 5 mL/hr for 48 hr. Use tubing that is sterile, non-pyrogenic, low protein-binding, with a 0.2 micron in-line filter. Ensure tubing is compatible with infusion pump.

Patient/Family Teaching

  • Explain schedule for blinatumomab administration. Instruct patient to reach Medication Guide before starting therapy and before each cycle in case of changes.
  • Instruct patient in how to keep area around IV catheter clean to reduce infections. Advise patient not to change settings of infusion pump.
  • May cause seizures and loss of consciousness. Caution patient to avoid driving or other activities requiring alertness until response from medication is known.
  • Advise patient to notify health care professional immediately if signs and symptoms of cytokine release syndrome (fever, tiredness or weakness, dizziness, headache, low blood pressure, nausea, vomiting, chills, facial swelling, wheezing or difficulty breathing, rash) or neurological problems (seizures, difficulty speaking or slurred speech, loss of consciousness, confusion, disorientation, loss of balance) or if side effects occur that are bothersome or persistent.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Decrease in progression of Philadelphia chromosome-negative relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL).
References in periodicals archive ?
BLINCYTO - Key Pipeline Products and Development a.
Food and Drug Administration today approved Blincyto (blinatumomab) to treat patients with Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.
Food and Drug Administration (FDA) has granted approval of BLINCYTO (blinatumomab) for the treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Growing Body of Clinical Evidence Validates Immunotherapy BLINCYTO (Blinatumomab) for Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia
We are pleased to receive positive CHMP opinions for Kyprolis and BLINCYTO as this is an important step in providing new treatment options for patients in Europe with rare forms of cancer," said Sean E.
Our study forecasts sales of 7 products, including these brands: - Adcetris - Kadcyla - Gazyva/Gazyvaro - Poteligeo - Removab - Blincyto - Kalbitor
Food and Drug Administration (FDA) approval of BLINCYTO for Philadelphia chromosome-negative relapsed/refractory B-precursor acute lymphoblastic leukemia.
With this approval, BLINCYTO becomes the first FDA-approved bispecific CD19-directed CD3 T cell engager (BiTE[sup.
The FDA also said yes to BioMarin's Vimizim for the treatment of Morquio A syndrome, Celgene's blockbuster hopeful Otezla and Amgen's leukemia drug, Blincyto.
Although the label comes with a boxed warning, approval came five months ahead of schedule (Read more: Amgen's Blincyto Gets FDA Nod, Carries Boxed Warning).