Bortezomib parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of bortezomib.
Drugs List
Therapeutic Indications
Uses
Mantle cell lymphoma (MCL)
Myeloma - multiple
Progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for haematopoietic stem cell transplantation. For monotherapy or in combination with pegylated liposomal doxorubicin or dexamethasone.
Previously untreated multiple myeloma who are not eligible for high-dose chemotherapy with haematopoietic stem cell transplantation. In combination with melphalan and prednisone.
Induction treatment of adult patients with previously untreated multiple myeloma who are eligible for high-dose chemotherapy with haematopoietic stem cell transplantation. In combination with dexamethasone or with dexamethasone and thalidomide.
Previously untreated mantle cell lymphoma who are unsuitable for haematopoietic stem cell transplantation. In combination with rituximab, cyclophosphamide, doxorubicin and prednisone.
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.
Patients with Hepatic Impairment
Moderate hepatic impairment or higher (Bilirubin level between above 1.5 times the upper limit of normal (ULN)
Reduce starting dose to 0.7 mg/metre square in the first treatment cycle. Consider dose escalation to 1 mg/metre square or further dose reduction to 0.5 mg/metre square in subsequent cycles based on patient tolerability.
Additional Dosage Information
Dose reduction levels of bortezomib
Full dose
1.3 mg/metre square.
1st reduction
1 mg/metre square.
2nd reduction
0.7 mg/metre square.
Dose reductions in all indications
Neuropathy
Grade 1 with pain or grade 2 (interferes with function but not with activities of daily living): Reduce dose to 1 mg/metre square or change treatment schedule to 1.3 mg/ metre square once weekly.
Grade 2 with pain or grade 3 (interfering with activities of daily living): Withhold treatment until symptoms of toxicity have resolved. Resume treatment at a dose of 0.7 mg/metre square once weekly.
Grade 4 (sensory neuropathy which is disabling or motor neuropathy that is life threatening or leads to paralysis or severe autonomic neuropathy): Discontinue treatment.
Grade 3 non-haematological (excluding neuropathies) or grade 4 haematological toxicities
Suspend treatment until symptoms of toxicity resolve. Re-initiate treatment at a dose reduced by one dose level. If the toxicity is not resolved or if it recurs at the lowest dose, discontinuation of bortezomib must be considered unless the benefit of treatment clearly outweighs the risk.
Multiple myeloma in combination with melphalan and prednisone
Prior to initiating a new cycle of therapy:
Platelet counts should be equal to or greater than 70 x 10 to the power 9/litre.
Absolute neutrophils count should be equal to or greater than 1 x 10 to the power 9/litre.
Non-haematological toxicities should have resolved to grade 1 or baseline.
Dose modifications during subsequent cycles
Prolonged grade 4 neutropenia or thrombocytopenia, or thrombocytopenia with bleeding: Consider reducing melphalan dose by 25% in the next cycle.
Platelet counts equal to or less than 30 x 10 to the power 9/litre or absolute neutrophil count equal to or less than 0.75 x 10 to the power 9/litre on bortezomib dosing days (other than day 1): Suspend treatment of bortezomib.
If several bortezomib doses are withheld in a cycle (greater than or equal to 3 during twice weekly administration or greater than or equal to 2 during weekly administration): Reduce dose by one dose level.
Non-haematological toxicities grade 3 and above: Suspend treatment until symptoms have resolved to grade 1 or baseline. Re-initiate treatment at a dose reduced by one dose level.
Combination therapy for the treatment of previously untreated mantle cell lymphoma
Prior to initiating a new cycle of therapy:
Platelet counts should be equal to or greater than 100 x 10 to the power 9/litre.
Platelet counts should be equal to or greater than 75 x 10 to the power 9/litre in patients with bone marrow infiltration or splenic sequestration.
Absolute neutrophils count should be equal to or greater than 1.5 x 10 to the power 9/litre.
Haemoglobin equal to or below 8g per dL.
Non-haematological toxicities should have resolved to grade 1 or baseline.
Dose modifications during subsequent cycles:
Grade 3 neutropenia with fever, Grade 4 neutropenia lasting more than 7 days or a platelet count less than 10 x 10 to the power 9/litre: Suspend treatment for up to 2 weeks until patient has an ANC of greater than 0.75 x 10 to the power 9/litre and platelet count 25 x to the power 9/litre. Discontinue if the toxicity does not resolve. If toxicity resolves within 2 weeks re-initiate treatment at a dose reduced by one dose level.
Platelet count less than 25 x 10 to the power 9/litre or ANC less than 0.75 x 10 to the power 9/litre: Suspend treatment until levels higher than these values.
Treatment related grade 3 or greater non-haematological toxicities: Suspend treatment until symptoms resolve to grade 2 or lower. Re-initiate treatment at a dose reduced by one dose level.
Administration
Bortezomib 3.5mg powder for solution for infusion for intravenous or subcutaneous use only.
Bortezomib 1mg powder for solution for infusion for intravenous use only.
The concentration after reconstitution determines the route of administration.
Contraindications
Children under 18 years
Acute diffuse infiltrative pulmonary disorder
Acute pericardial disorder
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Haemoglobin concentration below 8g / dL
Patients over 75 years
Predisposition to cardiac failure
Predisposition to haemorrhage
Predisposition to seizures
Predisposition to syncope
Autonomic neuropathy
Cardiac disorder
Congestive cardiac failure
Dehydration
Diabetes mellitus
Diabetic autonomic neuropathy
Electrolyte imbalance
History of hepatitis B
History of torsade de pointes
Moderate hepatic impairment
Neutropenia
Peripheral neuropathy
Renal impairment - creatinine clearance below 20ml/min/1.73m sq
Thrombocytopenia
Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Correct electrolyte disorders before treatment
Reduce dose in patients with moderate hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen at risk patients for hepatitis B infection
Herpes zoster reactivation possible - consider antiviral prophylaxis
Maintain adequate hydration of patient prior / during treatment
Prophylactic G-CSF should be considered
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Consider chest x-ray prior to initiating therapy
Consider monitoring ECG in patients at risk of QT prolongation
If dyspnoea occurs, investigate for signs of progressive pulmonary disorder
Monitor blood glucose closely in patients with diabetes mellitus
Monitor for signs of haematological and non-haematological toxicity
Monitor full blood count regularly
Monitor patient for signs of serious infection
Monitor patients experiencing constipation
Monitor patients for signs of tumour lysis syndrome
Monitor patients for symptoms of neuropathy
Monitor patients with cardiac disorders
Monitor patients with hepatic impairment for toxic effects
Monitor patients with high tumour burden closely during therapy
Monitor platelet count prior to each dose
Monitor renal function in patients with renal impairment
Monitor serum electrolytes
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of infection immediately
Advise patient to seek medical advice if signs of hypotension occur
Consider dose/ schedule adjustment if neuropathy occurs
Reactivation of hepatitis B may occur in chronic carriers
Reactivation of herpes zoster may occur
Consider suspending if significant drop in platelet/neutrophil count occurs
Consider treatment interruption & dose reduction in haematological toxicity
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if severe immunocomplex mediated reactions occur
Discontinue in grade 4 neuropathy
Concurrent anti-hypertensive medication may require adjustment
Advise patient not to take St John's wort concurrently
Advise patients to avoid vitamin C containing products
Advise patients to avoid green tea and green tea products
Male & female: Contraception required during & for 3 months after treatment
A chest X-ray should be performed before treatment to exclude the possibility of severe pulmonary disease and to serve as a baseline for potential pulmonary changes during and after treatment.
Treatment with bortezomib is associated with peripheral neuropathy, the incidence increases during early cycles, peaking in cycle 5.
Management of orthostatic/postural hypotension may require an adjustment of anti-hypertensive products, rehydration or administration of mineralocorticoids and/or sympathomimetics.
Patients receiving oral hypoglycaemics should have normal liver function confirmed and caution should be exercised, regular monitoring of blood glucose levels is recommended.
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.
Pregnancy and Lactation
Pregnancy
Bortezomib is contraindicated during pregnancy.
The manufacturer recommends that bortezomib is not used in pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. At the time of writing there is no data on the use of bortezomib in human pregnancy. Animal studies have shown growth restriction and an increased risk of postimplantation loss. Because the recommended dose is given over several weeks, use during pregnancy could result in multiple exposures of the embryo and/or foetus to a cytotoxic agent. However, if treatment is needed during pregnancy, the decision to use bortezomib should be made on a case-by-case basis. The women should be advised of the potential risk to her embryo and/or foetus.
Lactation
Bortezomib is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding is discontinued during treatment with bortezomib. It is unknown if bortezomib is excreted in human milk. There is a theoretical risk of excretion due to the molecular weight, the long elimination half-life, the moderate plasma protein binding and lack of rapid metabolism. A risk to neonates cannot be excluded.
Side Effects
Acute pancreatitis
Alkalosis
Angina pectoris
Arrhythmias
Asthenia
Attention disturbances
Bacteraemia
Blood disorders
Blood pressure changes
Cardiac arrest
Cardiac failure
Cardiac tamponade
Cardiogenic shock
Cerebral haemorrhage
Cerebrovascular accident
Changes in blood chemistry
Changes in mental activity
Chest discomfort
Cognitive impairment
Convulsions
Dehydration
Disturbances of appetite
Dizziness
Dream abnormalities
Dysaesthesia
Dysgeusia
Dyspnoea
Encephalopathy
Erectile dysfunction
Eye disorder
Facial oedema
Fatigue
Flushing
Gastro-intestinal symptoms
Glomerulonephritis
Haematoma
Hair disorder
Hallucinations
Headache
Hearing disturbances
Hepatic disorders
Herpes zoster
Hypersalivation
Hypersensitivity reactions
Hypoaesthesia
Inappropriate secretion of antidiuretic hormone
Influenza-like syndrome
Injection site reactions
Irritability
Ischaemic colitis
Lethargy
Loss of vision
Malaise
Migraine
Musculoskeletal disturbances
Myocardial infarction
Nail disorders
Nausea
Neuralgia
Night sweats
Oedema
Opportunistic infections
Optic neuritis
Pain
Paraesthesia
Paresis
Peripheral neuropathy
Peripheral oedema
Phlebitis
Photosensitivity
Pneumonia
Polyarthritis
Posterior reversible encephalopathy syndrome (PRES)
Pulmonary disorder
Pulmonary hypertension
Pulmonary oedema
Pyrexia
Rash
Renal disorders
Respiratory disorders
Restless legs
Sciatica
Sensation of cold
Sepsis
Serum sickness-like reactions
Skin disorder
Sleep disturbances
Speech disturbances
Stevens-Johnson syndrome
Syncope
Tenderness (non-specified)
Testicular pain
Tongue disorder
Toxic epidermal necrolysis
Tremor
Tumour lysis syndrome
Urinary abnormalities
Vascular disorders
Vertigo
Vomiting
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: May 2019
Reference Sources
Summary of Product Characteristics: Velcade 3.5mg powder for solution for injection. Janssen-Cilag Ltd. Revised February 2019
Summary of Product Characteristics: Bortezomib 3.5mg powder for solution for injection. Aspire Pharma. Revised June 2019
Summary of Product Characteristics: Bortezomib 2.5mg powder for solution for injection. Aspire Pharma. Revised June 2019
Summary of Product Characteristics: Bortezomib 1mg powder for solution for injection. Aspire Pharma. Revised June 2019
Summary of Product Characteristics: Bortezomib 3.5mg powder for solution for injection. Dr Reddy's Laboratories. Revised July 2019
Nature. Ascorbic acid inhibits antitumor activity of bortezomib in vivo.
Available at: https://www.nature.com/articles/leu200983
Last accessed: 19 August 2019
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 May 2019
PJ Online. Green tea could interfere with anticancer drug bortezomib.
Available at: https://www.pjonline.com/news/green_tea_could_interfere_with_anticancer_drug_bortezomib
Last accessed: October 6th 2011.
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.