Carfilzomib parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of carfilzomib.
Drugs List
Therapeutic Indications
Uses
Multiple myeloma: resistant to one previous therapy
Treatment of multiple myeloma in combination with lenalidomide and dexamethasone in adult patients who have received at least one prior therapy.
Treatment of multiple myeloma in combination with dexamethasone in adult patients who have received at least one prior therapy.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Doses are calculated using body surface area (BSA). Patients with a BSA greater than 2.2 metres squared should be treated based on a BSA of 2.2 metres squared.
Adults
In Combination with Lenalidomide and Dexamethasone
Cycle 1: Day 1 and 2 administer carfilzomib 20mg/metre squared (up to a maximum of 44mg). If well tolerated the subsequent doses should be increased to 27mg/metre squared (up to a maximum of 60mg) for day 8, 9, 15 and 16 followed by a 12 day rest period (days 17 to 28). Each 28 day period is considered one treatment cycle.
Cycles 2 to 12: Carfilzomib should be administered at 27mg/metre squared (up to a maximum of 60mg) on two consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, and 16) followed by a 12 day rest period (days 17 to 28).
Cycle 13 onwards: Carfilzomib should be administered at 27mg/metre squared (up to a maximum of 60mg) on days 1, 2, 15, and 16 followed by a 12 day rest period (days 17 to 28).
In Combination with Dexamethasone
Cycle 1: Day 1 and 2 administer carfilzomib 20mg/metre squared (up to a maximum of 44mg). If well tolerated the subsequent doses should be increased to 56 mg/metre squared (up to a maximum of 123mg) for day 8, 9, 15 and 16 followed by a 12 day rest period (days 17 to 28). Each 28 day period is considered one treatment cycle.
Cycles 2 onwards: Carfilzomib should be administered at 56mg/metre squared (up to a maximum of 123mg) on two consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, and 16) followed by a 12 day rest period (days 17 to 28).
Carfilzomib may be continued for longer than 18 cycles based on individual risk/benefit assessment, until disease progression or until unacceptable toxicity occurs.
Additional Dosage Information
Dose reductions
Dose reductions for the following are both considered 1 dose level reduction
If patient is on the 56mg/metre squared dose reduce to 45mg/metre squared
If patient is on the 45mg/metre squared dose reduce to 36mg/metre squared
If patient is on the 36mg/metre squared dose reduce to 27mg/metre squared
If patient is on the 27mg/metre squared dose reduce to 20mg/metre squared
If patient is on the 20mg/metre squared dose reduce to 15mg/metre squared
Absolute neutrophil count below 0.5 x 10 to the power of 9/L
First occurrence: Suspend treatment. Once recovered to equal to or greater than 0.5 x 10 to the power of 9/L restart at same dose level.
Subsequent occurrences: Suspend treatment. Once recovered to equal to or greater than 0.5 x 10 to the power of 9/L consider restarting at reduced dose level.
Febrile neutropenia (Absolute neutrophil count less than 0.5 x 10 to the power of 9 /L and an oral temperature above 38.5 degrees C or two consecutive readings of 38 degrees C for 2 hours)
Suspend treatment. Once recovered to baseline resume at the same dose level.
Platelet count below 10 x 10 to the power of 9/L or evidence of bleeding with thrombocytopenia
First occurrence: Suspend treatment. Once recovered to equal to or greater than 10 x 10 to the power of 9/L or bleeding controlled, continue treatment at same dose level.
Subsequent occurrences: Suspend treatment. Once recovered to equal to or greater than 10 x 10 to the power of 9/L consider restarting at reduced dose level.
Creatinine equal to or greater than 2x baseline
Suspend treatment and continue to monitor renal function. Once recovered to within 25% of baseline, consider restarting at reduced dose level.
Creatinine less than 15ml/minute (or creatinine clearance decreased to less than 50%) or need for dialysis
Suspend treatment and continue to monitor renal function. Once recovered to within 25% of baseline, consider restarting at reduced dose level.
Patients on dialysis should receive carfilzomib after dialysis.
Grade 3 or 4 non-haematologic toxicities
Suspend treatment. Once recovered to baseline, consider restarting at reduced dose level.
Administration
In Combination with Lenalidomide and Dexamethasone
To be administered intravenously as a 10 minute infusion.
In Combination with Dexamethasone
To be administered intravenously as a 30 minute infusion.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Asian ancestry
Disorder of fluid balance
Patients over 75 years
Predisposition to venous thromboembolism
Restricted sodium intake
Angina
Cardiac arrhythmias
Cardiac conduction defects
Dehydration
Hepatic impairment
Hepatitis B
Hypertension
New York Heart Association class III failure
New York Heart Association class IV failure
Renal impairment
Within 4 months of myocardial infarction
Haemodialysis patients: administer drug after dialysis
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Consider premedication with hypouricaemic agent
Consider use of anticoagulant prophylaxis if at risk of thromboembolism
Ensure hypertension is controlled prior to treatment
Herpes zoster reactivation possible - consider antiviral prophylaxis
Maintain adequate hydration of patient prior / during treatment
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
Assess baseline cardiac function prior to treatment
Monitor hepatic function before initiating and at monthly intervals
Monitor renal function before initiating and at monthly intervals
Consider PTLD or PML if new or worsening neurological symptoms occur
If dyspnoea occurs, investigate for signs of progressive pulmonary disorder
Monitor blood counts regularly
Monitor blood pressure
Monitor fluid balance
Monitor for and manage hepatitis reactivation during treatment
Monitor patient for infusion-associated reactions (IARs)
Monitor patients at risk for signs & symptoms of thromboembolism
Monitor patients for signs of adverse cardiovascular effects
Monitor patients for signs of tumour lysis syndrome
Monitor serum potassium regularly
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of thrombotic microangiopathy
Advise patients to report any signs of dyspnoea, chest pain or ankle oedema
Reactivation of hepatitis B may occur in chronic carriers
Reduce dose if hypertension cannot be controlled
Suspend treatment and investigate signs of pulmonary toxicity
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if thrombotic microangiopathy is confirmed
Hepatitis B reactivation: Suspend treatment and refer to liver specialist
Interrupt treatment if febrile neutropenia occurs
Suspend at first signs of thrombotic microangiopathy
Suspend therapy if neutrophils fall below 0.5 x 10 to the power of 9 / L
Suspend treatment and/or reduce dose if pulmonary hypertension occurs
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Suspend treatment and/or reduce dose in grade 3 or greater cardiac toxicity
Suspend treatment if hypertension cannot be controlled
Suspend treatment if platelets fall below 10 x 10 to the power of 9/L
Suspend treatment if serum creatinine greater than or equal to 2 x baseline
Suspend treatment if tumour lysis syndrome occurs
Female:Non-hormonal contraception advised until 1 month after treatment
Male: Contraception required during and for 3 months after treatment
Breastfeeding: Do not breastfeed & discard milk for 48 hours after therapy
As carfilzomib is used in combination, the information regarding those medicinal products should be consulted prior to their use.
Particular attention should be paid to the pregnancy testing and prevention requirements for use of lenalidomide.
Efficacy of oral contraceptives may decrease during treatment.
There is an increased risk of venous thromboembolic events associated with carfilzomib, the use of hormonal contraceptives with a risk of thrombosis should therefore be avoided during treatment.
Cardiac events such as cardiac arrest, myocardial infarction, and cardiac failure, including fatal cases, have been reported. Patients without a pre-existing cardiac disorder are also at risk of cardiac events.
Asian patients treated with carfilzomib have been shown to have an increased risk of cardiac failure.
Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
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.
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
Carfilzomib is contraindicated during pregnancy.
The manufacturer recommends carfilzomib should not be used during pregnancy unless the benefit outweighs the potential risk to the foetus. Foetal harm has been shown in animal studies. The effect of concurrent therapies must also be considered.
Lactation
Carfilzomib is contraindicated during breastfeeding.
The manufacturer recommends breastfeeding is stopped during and for 2 days after treatment. It is unknown if carfilzomib is excreted in human milk. A risk to the nursing infant cannot be excluded. The effect of concurrent therapies must also be considered.
Side Effects
Acute respiratory distress syndrome
Anaemia
Angioedema
Anxiety
Arthralgia
Asthenia
Atrial fibrillation
Blood pressure changes
Blurred vision
Cardiac arrest
Cardiac failure
Cataracts
Cerebrovascular accident
Chills
Cholestasis
Confusion
Constipation
Cough
Decrease in creatinine clearance
Decreased appetite
Decreased ejection fraction
Deep vein thrombosis (DVT)
Dehydration
Diarrhoea
Dizziness
Dyspepsia
Dysphonia
Dyspnoea
Electrolyte disturbances
Epistaxis
Erythema
Fatigue
Febrile neutropenia
Flushing
Gamma glutamyl transferase (GGT) increased
Gastro-enteritis
Gastro-intestinal perforation
Haemolytic uraemic syndrome
Haemorrhage
Headache
Hepatic failure
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertensive crisis
Hyperuricaemia
Hypoalbuminaemia
Hypoesthesia
Increase in serum ALT/AST
Infections
Influenza-like syndrome
Infusion-related symptoms
Insomnia
Interstitial lung disease
Leukopenia
Lymphopenia
Malaise
Multiorgan failure
Muscle spasm
Muscle weakness
Myalgia
Myocardial infarction
Myocardial ischaemia
Nausea
Neutropenia
Pain
Palpitations
Paraesthesia
Pericardial effusion
Pericarditis
Peripheral neuropathy
Peripheral oedema
Pneumonitis
Posterior reversible encephalopathy syndrome (PRES)
Progressive multifocal leukoencephalopathy (PML)
Prolongation of QT interval
Pruritus
Pulmonary embolism
Pulmonary hypertension
Pulmonary oedema
Pyrexia
Raised C-reactive protein
Rash
Reactivation of hepatitis B
Renal failure
Renal impairment
Respiratory failure
Respiratory tract infection
Sepsis
Serum bilirubin increased
Serum creatinine increased
Tachycardia
Thrombocytopenia
Thrombotic microangiopathy
Thrombotic thrombocytopenic purpura
Tinnitus
Tooth ache
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: November 2020
Reference Sources
Summary of Product Characteristics: Kyprolis powder for solution for infusion. Amgen Ltd. Revised June 2020.
MHRA Drug Safety Update August 2019
Available at: https://www.mhra.gov.uk
Last accessed: 05 September 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.