Drug Action
Carfilzomib is an irreversible selective proteasome inhibitor that disrupts tumour cell turnover and induces apoptosis.
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Drug reference
Carfilzomib is an irreversible selective proteasome inhibitor that disrupts tumour cell turnover and induces apoptosis.
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Treatment of multiple myeloma in patients who have received at least one prior therapy (in combination with dexamethasone, or with dexamethasone and lenalidomide) (specialist use only) ▶BY INTRAVENOUS INFUSION ▶Adult: (consult product literature or local protocols) Immune system and malignant disease
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Elderly (over 75 years)—higher incidence of adverse effects. ensure adequate hydration. infusion- related reactions. recent history of myocardial infarction. risk of cardiac failure. risk of herpes zoster reactivation. uncontrolled angina. uncontrolled arrhythmias CAUTIONS, FURTHER INFORMATION ▶Infusion-related reactions Manufacturer advises premedication with dexamethasone to reduce incidence and severity of infusion-related reactions. ▶Risk of herpes zoster reactivation Manufacturer advises consider antiviral prophylaxis for herpes zoster infection.
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NICE decisions ▶Carfilzomib for previously treated multiple myeloma (July 2017) NICE TA457 Carfilzomib (Kyprolis ®) in combination with dexamethasone is recommended as an option for treating multiple myeloma in adults, only if: . they have had only 1 previous therapy, which did not include bortezomib, and . the manufacturer provides carfilzomib with the discount agreed in the patient access scheme. Patients currently receiving carfilzomib whose disease does not meet the above criteria should have the option to continue their treatment until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta457 Scottish Medicines Consortium (SMC) decisions SMC No. 1171/16 The Scottish Medicines Consortium has advised (January 2017) that carfilzomib (Kyprolis ®) in combination with lenalidomide and dexamethasone is not recommended for use within NHS Scotland for the treatment of adults with multiple myeloma who have received at least one prior therapy as the economic case was not demonstrated. SMC No. 1242/17 The Scottish Medicines Consortium has advised (August 2017) that carfilzomib (Kyprolis ®) is accepted for use within NHS Scotland, in combination with dexamethasone alone for the treatment of adults with multiple myeloma who have received at least one prior therapy. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower.
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MHRA/CHM ADVICE: CARFILZOMIB (KYPROLIS ®): REMINDER OF RISK OF POTENTIALLY FATAL CARDIAC EVENTS (AUGUST 2019) Cases of cardiac arrest, cardiac failure, and myocardial infarction, including fatalities, have been reported in patients with or without pre-existing cardiac disorders receiving carfilzomib. Healthcare professionals are advised to monitor patients for signs and symptoms of cardiac disorders before and during carfilzomib treatment. Carfilzomib should be discontinued if severe or life-threatening cardiac events occur; restarting treatment may be considered at a lower dose once the condition is controlled and the patient is stable. MHRA/CHM ADVICE: CARFILZOMIB (KYPROLIS ®): RISK OF REACTIVATION OF HEPATITIS B VIRUS (NOVEMBER 2019) An EU review of worldwide data has identified reports of hepatitis B virus (HBV) reactivation in patients treated with carfilzomib. Healthcare professionals are advised to screen all patients for HBV before initiating treatment; those with unknown serology already being treated with carfilzomib should also be screened. Patients with positive serology should be considered for antiviral prophylaxis, and be monitored for signs of HBV reactivation during and after treatment; immediate medical attention should be sought if signs and symptoms of HBV reactivation develop. Experts should be consulted for advice about HBV treatment and the continuation, interruption, or resumption of carfilzomib in patients with HBV reactivation.
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→Appendix 1: carfilzomib
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▶Common or very common Anaemia. anxiety. appetite decreased. arrhythmias. arthralgia. asthenia. cataract. chest pain. chills. confusion. constipation. cough. decreased leucocytes. dehydration. diarrhoea. dizziness. dysphonia. dyspnoea. electrolyte imbalance. embolism and thrombosis. fever. flushing. gastrointestinal discomfort. haemorrhage. headache. heart failure. hyperbilirubinaemia. hyperglycaemia. hyperhidrosis. hypertension. hyperuricaemia. hypoalbuminaemia. hypotension. increased risk of infection. influenza like illness. infusion related reaction. insomnia. malaise. muscle complaints. muscle weakness. myocardial infarction. nausea. neutropenia. oropharyngeal pain. pain. palpitations. peripheral neuropathy. peripheral oedema. pulmonary hypertension. pulmonary oedema. renal impairment. respiratory disorders. sensation abnormal. sepsis. skin reactions. thrombocytopenia. tinnitus. toothache. vision blurred. vomiting ▶Uncommon Cardiac arrest. Clostridioides difficile colitis. gastrointestinal perforation. haemolytic uraemic syndrome. hepatic disorders. hepatitis B reactivation. intracranial haemorrhage. multiple organ dysfunction syndrome. myocardial ischaemia. pericardial effusion. pericarditis. stroke. tumour lysis syndrome ▶Rare or very rare Angioedema. posterior reversible encephalopathy syndrome (PRES). thrombotic microangiopathy ▶Frequency not known Progressive multifocal leukoencephalopathy (PML). QT interval prolongation
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Manufacturer recommends effective contraception during and for 1 month after treatment in women of childbearing potential; hormonal contraceptives associated with a risk of thrombosis should be avoided. Male patients should use effective contraception during and for 3 months after treatment if their partner is pregnant or of childbearing potential. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Manufacturer advises avoid unless potential benefit outweighs risk—toxicity in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Manufacturer advises avoid during and for at least 2 days after treatment—no information available.
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Manufacturer advises caution (increased risk of side-effects), particularly in moderate to severe impairment (limited information available).
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Manufacturer advises caution— increased incidence of adverse effects.
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Manufacturer advises monitoring of the following patient parameters: serum potassium concentration at least monthly; signs and symptoms of fluid overload, especially in those at risk of cardiac failure; renal function at treatment initiation and at least monthly during treatment—consider dose modification; hepatic function at treatment initiation and monthly during treatment—consider dose modification; platelet count and blood pressure. Also monitor for signs and symptoms of thrombotic microangiopathy. l HANDLING AND STORAGE Manufacturer advises store in a refrigerator at 2–8°C.
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There can be variation in the licensing of different medicines containing the same drug. Powder for solution for infusion ELECTROLYTES: May contain Sodium ▶Kyprolis (Amgen Ltd) A Carfilzomib 10 mg Kyprolis 10mg powder for solution for infusion vials | 1 vial P £176.00 Carfilzomib 30 mg Kyprolis 30mg powder for solution for infusion vials | 1 vial P £528.00 Carfilzomib 60 mg Kyprolis 60mg powder for solution for infusion vials | 1 vial P £1,056.00
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Manufacturer advises that patients and carers are warned to report signs and symptoms of thromboembolism (such as dyspnoea, chest pain, arm or leg swelling or pain). Driving and skilled tasks Patients and their carers should be counselled on the effects on driving and skilled tasks— increased risk of dizziness, hypotension and blurred vision.
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(consult product literature or local protocols)
First-line fragment. Read the complete Indications and Dose section above.
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