Blinatumomab

Blinatumomab is a prescription medication used to treat the symptoms of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). 

• Blinatumomab is available under the following different brand names: Blincyto

Adult and pediatric dosage

Injection, lyophilized powder for reconstitution

• 35mcg/vial

Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

Adult dosage

• Adult below 45 kg (BSA-based dose)
• Induction (Cycle 1)
  • Days 1-7: 5 mcg/m2/day continuous Intravenous 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 Intravenous 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 Intravenous 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 Intravenous infusion (not to exceed 28 mcg/day), THEN  
  • Days 29-84: treatment-free interval
• Adult above 45 kg (fixed dose)
• Induction (Cycle 1)
  • Days 1-7: 9 mcg/day continuous Intravenous infusion, THEN
  • Days 8-28: 28 mcg/day
  • Days 29-42: treatment-free interval
• Induction (Cycle 2)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion, THEN
  • Days 29-42: treatment-free interval
• Consolidation (Cycles 3-5)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion
  • Days 29-42: treatment-free interval
• Continued therapy (Cycles 6-9)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion
  • Days 29-84: treatment-free interval

Pediatric dosage

Children below 45 kg (BSA-based dose)

• Induction (Cycle 1)
  • Days 1-7: 5 mcg/m2/day continuous Intravenous 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 Intravenous 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 Intravenous 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 Intravenous infusion (not to exceed 28 mcg/day), THEN  
  • Days 29-84: treatment-free interval
• Children above 45 kg (fixed dose)
• Induction (Cycle 1)
  • Days 1-7: 9 mcg/day continuous Intravenous infusion, THEN
  • Days 8-28: 28 mcg/day
  • Days 29-42: treatment-free interval
• Induction (Cycle 2)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion, THEN
  • Days 29-42: treatment-free interval
• Consolidation (Cycles 3-5)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion
  • Days 29-42: treatment-free interval
• Continued therapy (Cycles 6-9)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion
  • Days 29-84: treatment-free interval

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

Adult dosage

• Adult below 45 kg (BSA-based dose)
• Induction (Cycle 1)
  • Day 1-28: 15 mcg/m2/day continuous Intravenous 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 Intravenous infusion; not to exceed 28 mcg/day  
  • Days 29-42: treatment-free interval
• Adult above 45 kg (fixed dose)
• Induction (Cycle 1)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion  
  • Days 29-42: treatment-free interval
• Consolidation (Cycles 2-4)
  • Days 1-28: 28 mcg/day continuous Intravenous infusion  
  • Day 29-84: treatment-free interval

Pediatric dosage

• Children below 45 kg (BSA-based dose)
• Induction (Cycle 1)
  • Day 1-28: 15 mcg/m2/day continuous Intravenous 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 Intravenous infusion; not to exceed 28 mcg/day  
  • Days 29-42: treatment-free interval
• Children above 45 kg (fixed dose)
• Induction (Cycle 1)
  • Days 1-28: 28 mcg/m2/day continuous Intravenous infusion  
  • Days 29-42: treatment-free interval
• Consolidation (Cycles 2-4)
  • Days 1-28: 28 mcg/m2/day continuous Intravenous infusion  
  • Day 29-84: treatment-free interval

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Blinatumomab include:

• fever
• headache
• swelling of the extremities
• nausea
• tremor
• rash
• constipation
• fever accompanying low levels of white blood cells (febrile neutropenia), and
• low levels of potassium in the blood (hypokalemia)
• anemia
• low platelet levels in the blood
• low white blood cell count
• irregular heartbeats (arrhythmia)
• diarrhea
• abdominal pain
• vomiting
• fatigue
• chills
• chest pain
• infections
• weight gain
• decreased appetite
• back pain
• pain in extremities
• bone pain
• joint pain
• dizziness
• insomnia
• cough
• shortness of breath
• nosebleeds
• high or low blood pressure (hypertension or hypotension)

Serious side effects of Blinatumomab include:

• fever
• chills
• trouble breathing
• body aches
• vomiting
• diarrhea, or
• feeling light-headed.

Rare side effects of Blinatumomab include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Blinatumomab has severe interactions with no other drugs
• Blinatumomab has serious interactions with the following drugs:
  • ropeginterferon alfa 2b
  • sirolimus
• Blinatumomab has moderate interactions with the following drugs:
  • Carbamazepine
  • Clonidine
  • Cyclosporine
  • Dichlorphenamide
  • Disopyramide
  • Ethosuximide
  • Fosphenytoin
  • ofatumumab SC
  • phenobarbital
  • phenytoin
  • primidone
  • quinidine
  • quinine
  • Siponimod
  • Tacrolimus
  • Theophylline
  • Trastuzumab
  • trastuzumab deruxtecan
  • valproic acid
• Blinatumomab has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to blinatumomab or any components of product formulation

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Blinatumomab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Blinatumomab?”

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 before starting of and during treatment (see Black Box Warnings)
• Neurological toxicities have occurred in approximately 65% of patients; the median time to the first event was within the first 2 weeks of treatment and the majority of events resolved; above Grade 3 (severe, life-threatening, or fatal) neurological toxicities occurred in approximately 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 pre-treatment 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, are 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 above 5 times ULN or if bilirubin rises to above 3 times ULN
• Leukoencephalopathy observed confirmed by cranial MRI, especially in patients with prior treatment with cranial irradiation and antileukemic chemotherapy (high dose methotrexate, IT cytarabine); the 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 is not recommended for at least 2 weeks before the start of treatment, during treatment, and until immune recovery following the last cycle of blinatumomab
• Fatal pancreatitis reported in combination with dexamethasone in clinical trials and post-marketing settings; 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 preservatives may cause serious adverse reactions (e.g., 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 the 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 (. g, warfarin) or drug concentrations (. g, cyclosporine)
  • Adjust the dose of the concomitant drug as needed

Pregnancy & Lactation

• Based on the mechanism of action, therapy may cause fetal harm when administered to the pregnant woman; verify the pregnancy status of females of reproductive potential before initiating treatment
• Due to the 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 the presence of blinatumomab in human milk, its effects on breastfed infants, or its effects on milk production; because many drugs are excreted in human milk and because of the 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