Blinatumomab parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of blinatumomab.
Drugs List
Therapeutic Indications
Uses
Philadelphia chromosome negative acute lymphoblastic leukaemia
Monotherapy for adults with CD19 positive relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL) and with Philadelphia chromosome positive B-precursor acute lymphoblastic leukaemia (ALL) should have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
Monotherapy for adults with Philadelphia chromosome negative CD19 positive B-cell precursor acute lymphoblastic leukaemia (ALL) in complete remission with minimal residual disease (MRD) equal to or greater than 0.1%.
Monotherapy for paediatric patients aged 1 or older with Philadelphia chromosome negative CD19 positive B-cell precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic haematopoietic stem cell transplantation.
Dosage
Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Additional Dosage Information
For patients with greater than or equal to 50% leukaemic blasts in bone marrow or greater than 15,000/microlitre peripheral blood leukaemic blast counts treat with dexamethasone (not to exceed 24 mg/day).
Treatment may be stopped temporarily or permanently following severe (grade 3) or life-threatening (grade 4) adverse effects. Treatment interrupted for no longer than 7 days, should continue the same 28 day treatment cycle. Treatment interrupted for more than 7 days, start a new cycle. Discontinue treatment permanently if toxicity takes greater than 14 days to resolve.
Cytokine release syndrome / tumour lysis syndrome
Patients greater than or equal to 45kg
Grade 3: Interrupt treatment until resolved then restart at 9micrograms/day. Escalate to 28micrograms/day after 7 days if toxicity does not reoccur.
Grade 4: Discontinue permanently.
Patients less than 45kg
Grade 3: Interrupt treatment until resolved then restart at 5micrograms/metre squared/day. Escalate to 15micrograms/metre squared/day after 7 days if toxicity does not reoccur.
Grade 4: Discontinue permanently.
Neurological toxicity
Convulsions: Discontinue permanently if more than 1 convulsion occurs. In the event of a seizure, prophylaxis with an anticonvulsant is recommended.
Patients greater than or equal to 45kg
Grade 3: Interrupt treatment until recovered to grade 1 or below for 3 days. Restart at 9micrograms/day, escalate to 28micrograms/day after 7 days if toxicity does not reoccur. When restarting treatment, premedicate with dexamethasone. If toxicity occurs at 9micrograms /day, or does not resolve after 7 days, discontinue permanently.
Grade 4: Discontinue permanently.
Patients less than 45kg
Grade 3: Interrupt treatment until recovered to grade 1 or below for 3 days. Restart at 5micrograms/metre squared/day, escalate to 15micrograms/metre squared/day after 7 days if toxicity does not reoccur. If toxicity occurs at 5micrograms/metre squared/day, or does not resolve after 7 days, discontinue permanently.
Grade 4: Discontinue permanently.
Elevated Liver enzymes
Patients greater than or equal to 45kg
Grade 3: Interrupt until resolved to grade 1 or below, then restart at 9micrograms/day. Escalate to 28micrograms/day after 7 days if toxicity does not reoccur.
Grade 4: Consider discontinuing permanently.
Patients less than 45kg
Grade 3: Interrupt until resolved to grade 1 or below, then restart at 5micrograms/metre squared/day. Escalate to 15micrograms/metre squared/day after 7 days if toxicity does not reoccur.
Grade 4: Consider discontinuing permanently.
Other adverse reactions
Patients greater than or equal to 45kg
Grade 3: Interrupt until resolved to grade 1 or below, then restart at 9micrograms/day. Escalate to 28micrograms/day after 7 days if toxicity does not reoccur.
Grade 4: Consider discontinuing permanently.
Patients less than 45kg
Grade 3: Interrupt until resolved to grade 1 or below, then restart at 5micrograms/metre squared/day. Escalate to 15micrograms/metre squared/day after 7 days if toxicity does not reoccur.
Grade 4: Consider discontinuing permanently.
Administration
To be administered as a continuous intravenous infusion at 1 of 4 defined flow rates over the period of treatment (see manufacturers information for more details).
Contraindications
Children under 1 year
Within 2 weeks of live viral or live bacterial vaccination
Breastfeeding
Pregnancy
Precautions and Warnings
Acute infection
Females of childbearing potential
Active ALL in CNS or cerebrospinal fluid
Central nervous system disorder
Dehydration
History of neurological disorder
Severe hepatic impairment
Severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Intrathecal chemotherapy prophylaxis is recommended
Maintain adequate hydration of patient prior / during treatment
Premedicate with a hypouricaemic agent
Premedicate with IV steroid 1 hour before each cycle
Premedication with antipyretic recommended
Treatment to be initiated and supervised by a specialist
May contain polysorbate
Consult local policy on the safe use of anti-cancer drugs
Infuse through a dedicated lumen
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Pre-treatment neurological examination recommended
Monitor blood counts regularly
Monitor for signs and symptoms of pancreatitis
Monitor for signs of neurological toxicity
Monitor patient constantly for signs of new infection
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of tumour lysis syndrome
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider discontinuation if pancreatitis occurs
Discontinue if severe cytokine release syndrome develops
Discontinue or suspend treatment if grade 4 toxicities occur
Discontinue if convulsions occur
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Female: Contraception required during and for 48 hours after treatment
Breastfeeding: Do not breastfeed & discard milk for 48 hours after therapy
There is limited experience in patients with active ALL in the central nervous system (CNS) or cerebrospinal fluid (CSF). However patients have been treated following the clearance of CSF blasts with CNS directed therapy (such as intrathecal chemotherapy). Patients may therefore be treated once the CSF is clear.
Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.
Pregnancy and Lactation
Pregnancy
Blinatumomab is contraindicated during pregnancy.
The manufacturer does not recommend using blinatumomab during pregnancy unless the potential benefit outweighs the potential risk to the foetus. Animal studies did not shown teratogenicity or embryotoxicity effects. Human data is limited and as such a potential risk cannot be ruled out. Exposure to blinatumomab may deplete B-cells in newborns, monitoring is recommended. Treatment with live virus in exposed newborns vaccines should be postponed until B-cell count has recovered.
The effect of concurrent therapies must also be considered.
Lactation
Blinatumomab is contraindicated during breastfeeding.
Use of blinatumomab when breastfeeding is contraindicated by the manufacturer. The presence of blinatumomab in human breast milk is unknown but due to its large molecular weight, transfer is not expected. Effects on exposed infants is unknown.
The effect of concurrent therapies must also be considered.
Side Effects
Abdominal pain
Anaemia
Aphasia
Arthralgia
Back pain
Bone pain
Capillary leak syndrome
Chest pain
Chills
Cognitive impairment
Confusion
Constipation
Convulsions
Cough
Cranial nerve disorder
Cytokine release syndrome
Cytokine storm
Decreased appetite
Diarrhoea
Disorientation
Dizziness
Dyspnoea
Encephalopathy
Facial oedema
Fatigue
Febrile neutropenia
Flushing
Gamma glutamyl transferase (GGT) increased
Headache
Hyperglycaemia
Hypersensitivity reactions
Hypertension
Hypoalbuminaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Hypotension
Immunoglobulin abnormalities
Impaired memory
Increase in serum ALT/AST
Infections
Infusion related reaction
Insomnia
Leukocytosis
Leukopenia
Lymphopenia
Nausea
Neurological effects
Neutropenia
Oedema
Painful extremities
Pancreatitis
Paraesthesia
Peripheral oedema
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Pyrexia
Rash
Sepsis
Serum bilirubin increased
Tachycardia
Thrombocytopenia
Tremor
Tumour lysis syndrome
Vomiting
Wheezing
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2021
Reference Sources
Summary of Product Characteristics: Blincyto 38.5micrograms powder for concentrate and solution for infusion. Amgen Ltd. Revised December 2020.
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