Brentuximab vedotin parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of brentuximab vedotin.
These products have been produced by recombinant technology using Chinese Hamster Ovary (CHO) cell lines.
Drugs List
Therapeutic Indications
Uses
CD30+ Hodgkin lymphoma
Systemic anaplastic large cell lymphoma (sALCL)
Treatment of cutaneous T-cell lymphoma
Treatment of previously untreated CD30+ Stage IV Hodgkin lymphoma (HL) in combination with doxorubicin, vinblastine and dacarbazine (AVD).
Treatment of relapsed or refractory CD30+ Hodgkin lymphoma (HL), in patients: Following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not an option.
Treatment of adult patients with CD30+ Hodgkin lymphoma (HL) at increased risk of relapse or progression following ASCT.
Treatment of adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) in combination with cyclophosphamide, doxorubicin and prednisone (CHP).
Treatment of relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).
Treatment of adult patients with CD30+ cutaneous T-cell lymphoma (CTCL) after at least 1 prior systemic therapy.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Treatment should be continued until disease progression or unacceptable toxicity.
Adults
Previously untreated HL
The recommended dose is 1.2mg/kg over 30 minutes on days 1 and 15 of each 28-day cycle, for 6 cycles.
CD30+ Hodgkin lymphoma (HL) at increased risk of relapse or progression
The recommended dose is 1.8mg/kg over 30 minutes once every 3 weeks, for up to 16 cycles.
Relapsed or refractory CD30+ Hodgkin lymphoma (HL)
The recommended dose is 1.8mg/kg over 30 minutes once every 3 weeks, for a minimum of 8 cycles and up to a maximum of 16 cycles.
Previously untreated systemic anaplastic large cell lymphoma (sALCL)
The recommended dose is 1.8mg/kg over 30 minutes once every 3 weeks, for 6 to 8 cycles.
Relapsed or refractory systemic anaplastic large cell lymphoma (sALCL)
The recommended dose is 1.8mg/kg over 30 minutes once every 3 weeks, for a minimum of 8 cycles and up to a maximum of 16 cycles.
CD30+ cutaneous T-cell lymphoma (CTCL)
The recommended dose is 1.8mg/kg over 30 minutes once every 3 weeks, for up to 16 cycles.
Patients with HL or sALCL who have previously responded to treatment with brentuximab vedotin may resume treatment at the last indicated dose.
A maximum total dose of 180mg should be used for patients 100kg and over.
Patients with Renal Impairment
Combination therapy
Severe renal impairment: Treatment should be avoided.
Monotherapy
Creatinine clearance greater than 30ml/minute: Dose as normal (See Dosage; Adults).
Severe renal impairment: 1.2mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.
Patients with Hepatic Impairment
Combination therapy
Previously untreated sALCL in combination with CHP
Mild hepatic impairment: Starting dose of 1.2mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.
Moderate/severe hepatic impairment: Treatment should be avoided.
Previously untreated HL in combination with AVD
Mild hepatic impairment: Starting dose of 0.9mg/kg administered as an intravenous infusion over 30 minutes every 2 weeks.
Moderate/severe hepatic impairment: Treatment should be avoided.
Monotherapy
Starting dose of 1.2mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.
Additional Dosage Information
Dose modification for neutropenia with monotherapy
Grade 1 (greater than 1.5 x 10 to the power 9/litre) or Grade 2 (1.5 to 1 x 10 to the power of 9/litre): Continue treatment.
Grade 3 (1 to 0.5 x 10 to the power of 9/litre): Withhold dose until toxicity returns to Grade 2 or baseline then resume treatment at previous dose and schedule.
Patients who develop Grade 3 lymphopenia may continue treatment without interruption.
Grade 4 (less than 0.5 x 10 to the power of 9/litre): Withhold dose until toxicity returns to Grade 2 or baseline then resume treatment at previous dose and schedule.
Patients who develop Grade 4 lymphopenia may continue treatment without interruption.
Consider growth factor support in subsequent cycles for patients who develop Grade 3 or 4 neutropenia.
Dose modification for neutropenia with combination therapy
Grade 1 to 4 (greater than 1.5 x 10 to the power 9/litre to less than 0.5 x 10 to the power 9/litre): Prophylaxis with G-CSF from the first dose. Continue with the same dose and schedule.
Dose modification for peripheral neuropathy with monotherapy
Grade 1 (paraesthesia and/or loss of reflexes, with no loss of function): Continue treatment.
Grade 2 (interfering with function but not with activities of daily living) or Grade 3 (interfering with activities of daily living): Withhold dose until toxicity returns to Grade 1 or baseline, then restart treatment at a reduced dose of 1.2mg/kg every 3 weeks.
Grade 4 (sensory neuropathy which is disabling or motor neuropathy that is life threatening or leads to paralysis): Discontinue treatment permanently.
Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
Dose modification for peripheral neuropathy in combination therapy with AVD
Grade 1 (paraesthesia and/or loss of reflexes, with no loss of function): Continue treatment.
Grade 2 (interfering with function but not with activities of daily living): Reduce dose to 0.9mg/kg up to a maximum of 90mg every 2 weeks.
Administration
For intravenous infusion, over 30 minutes.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Body mass index above 30kg per square metre
Restricted sodium intake
Dehydration
Diabetes mellitus
Hepatic impairment
Renal impairment
Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Reduce dose in patients with creatinine clearance below 30ml/min
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consider premedication with hypouricaemic agent
Give pre-treatment counselling and consideration of sperm cryopreservation
Maintain adequate hydration of patient prior / during treatment
Premedicate all patients with prior infusion related reactions
Prophylactic G-CSF should be considered
Consult local policy on the safe use of anti-cancer drugs
Interrupt treatment if infusion reaction occurs & monitor until resolution
Never rechallenge treatment after a severe hypersensitivity reaction
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Monitor hepatic function before treatment and regularly during treatment
Monitor and manage cytomegalovirus reactivation during treatment
Monitor closely patient with pre-existing renal impairment
Monitor complete blood counts before each dose
Monitor for gastrointestinal toxicity
Monitor for symptoms of peripheral neuropathy
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of tumour lysis syndrome
Monitor serum glucose closely in all who experience a hyperglycaemic event
Patients with new pulmonary symptoms should be investigated
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue treatment if DRESS is confirmed
Discontinue treatment if Stevens-Johnson syndrome is confirmed
Discontinue treatment if toxic epidermal necrolysis is confirmed
Risk of developing opportunistic infections
Discontinue if pancreatitis occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue in grade 4 neuropathy
Interrupt therapy if neutrophil count <1.0x10 to the power 9/L
Suspend treatment and/or reduce dose if grade 3 or greater neutropenia
Suspend treatment if grade 2 or 3 neuropathy
Dose calculations for patients >100kg should use a maximum weight of 100kg
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Two reliable methods of contraception should be used simultaneously
Male & female: Contraception required during & for 6 months after treatment
Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with brentuximab vedotin. 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 brentuximab vedotin treatment should be permanently discontinued.
Cases of pulmonary toxicity have been reported in patients treated with brentuximab. In the event of new or worsening pulmonary symptoms a prompt diagnostic evaluation should be performed and a patients treated appropriately.
CD30+ CTCL
Brentuximab should be used with caution in CD30+ CTCL patients other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) after careful consideration of the potential benefit-risk on an individual basis.
Pregnancy and Lactation
Pregnancy
Brentuximab is contraindicated during pregnancy.
The manufacturer does not recommend using brentuximab vedotin during pregnancy.
At the time of writing there is no adequate data from the use of brentuximab in human pregnancy. Animal studies have shown reproductive toxicity.
Lactation
Brentuximab is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues brentuximab vedotin or discontinues breastfeeding.
It is not known whether brentuximab is excreted into human breast milk. A risk to neonates cannot be excluded.
Side Effects
Abdominal pain
Acute pancreatitis
Alopecia
Anaemia
Anaphylaxis
Arthralgia
Back pain
Candidiasis
Chills
Constipation
Cough
Cytomegalovirus infection
Decreased appetite
Demyelinating polyneuropathy
Development of neutralising antibodies
Diarrhoea
Dizziness
Dyspnoea
Enterocolitis
Erosion
Fatigue
Febrile neutropenia
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal ulceration
Herpes simplex
Herpes zoster
Hyperglycaemia
Ileus
Increase in serum ALT/AST
Increased susceptibility to infection
Infusion-related symptoms
Insomnia
Intestinal obstruction
Myalgia
Nausea
Neutropenia
Neutropenic colitis
Peripheral motor neuropathy
Peripheral sensory neuropathy
Pneumonia
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pyrexia
Rash
Sepsis
Staphylococcal infection
Stevens-Johnson syndrome
Thrombocytopenia
Toxic epidermal necrolysis
Tumour lysis syndrome
Upper respiratory tract infection
Vomiting
Weight loss
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: October 2019
Reference Sources
Summary of Product Characteristics: Adcetris 50mg powder for concentration for solution for infusion. Takeda UK Ltd. Revised December 2021.
The Renal Drug Handbook. Fourth edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 October 2019.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.