Carfilzomib


Concise Prescribing Info
Indications/Uses
Multiple myeloma.
Dosage/Direction for Use
Adult : IV For patients with relapsed or refractory multiple myeloma who received at least 1 prior treatment: Dosage is individualised according to patient’s baseline BSA. As monotherapy with dexamethasone premedication: 20 mg/m2 via infusion over 10 minutes, increase dose to 27 mg/m2 on day 8 of cycle 1 if tolerated. Withhold dose if severe toxicity occurs, then resume with 20 mg/m2 dose upon recovery. Alternatively, 20 mg/m2 via infusion over 30 minutes, increase dose to 56 mg/m2 on day 8 of cycle 1 if tolerated. Withhold dose if severe toxicity occurs, then resume with 45 mg/m2 dose upon recovery. Further reduce dose to 36 mg/m2 then to 27 mg/m2 if toxicity recurs. Omit doses on days 8 and 9 of cycle 13 onwards. Continue therapy until disease progression or unacceptable toxicity occurs. Discontinue treatment if toxicity persists. In combination with lenalidomide and dexamethasone: Initial: 20 mg/m2 (Max: 44 mg) via infusion over 10 minutes on days 1 and 2 of cycle 1, may increase dose to 27 mg/m2 (Max: 60 mg) on day 8 of cycle 1 if tolerated. Omit doses on days 8 and 9 of cycle 13 onwards. Treatment duration: 18 cycles. In combination with dexamethasone: Initially, 20 mg/m2 (Max: 44 mg) via infusion over 30 minutes on days 1 and 2 of cycle 1, may increase dose to 56 mg/m2 (Max: 123 mg) on day 8 of cycle 1 if tolerated. Continue treatment until disease progression or until unacceptable toxicity occurs. All doses are given on 2 consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, 16) followed by 12-day rest period (days 17-28). Each 28-day period is considered 1 treatment cycle. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Dosage Details
Intravenous
Multiple myeloma
Adult: For patients with relapsed or refractory multiple myeloma who received at least 1 prior treatment: Dosage is individualised according to patient’s baseline BSA. As monotherapy with dexamethasone premedication: 20 mg/m2 via infusion over 10 minutes, increase dose to 27 mg/m2 on day 8 of cycle 1 if tolerated. Withhold dose if severe toxicity occurs, then resume with 20 mg/m2 dose upon recovery. Alternatively, 20 mg/m2 via infusion over 30 minutes, increase dose to 56 mg/m2 on day 8 of cycle 1 if tolerated. Withhold dose if severe toxicity occurs, then resume with 45 mg/m dose upon recovery. Further reduce dose to 36 mg/m2 then to 27 mg/m2 if toxicity recurs. Omit doses on days 8 and 9 of cycle 13 onwards. Continue therapy until disease progression or unacceptable toxicity occurs. Discontinue treatment if toxicity persists. In combination with lenalidomide and dexamethasone: Initially, 20 mg/m2 (Max: 44 mg) via infusion over 10 minutes on days 1 and 2 of cycle 1, may increase dose to 27 mg/m2 (Max: 60 mg) on day 8 of cycle 1 if tolerated. Omit doses on days 8 and 9 of cycle 13 onwards. Treatment duration: 18 cycles. In combination with dexamethasone: Initially, 20 mg/m2 (Max: 44 mg) via infusion over 30 minutes on days 1 and 2 of cycle 1, may increase dose to 56 mg/m2 (Max: 123 mg) on day 8 of cycle 1 if tolerated. Continue treatment until disease progression or until unacceptable toxicity occurs. All doses are given on 2 consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15, 16) followed by 12-day rest period (days 17-28). Each 28-day period is considered 1 treatment cycle. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal Impairment
ESRD: Administer after haemodialysis.
Hepatic Impairment
Mild to moderate: Reduce dose by 25%.
Reconstitution
Dilute vial labelled as 60 mg, 30 mg and 10 mg with 29 mL, 15 mL and 5 mL sterile water for injection, respectively, to a final concentration of 2 mg/mL. May further dilute dose with 50-100 mL of 5% dextrose.
Contraindications
Pregnancy and lactation. Concomitant use with melphalan and prednisone.
Special Precautions
Patient with cardiac disorders (e.g. heart failure, recent MI, uncontrolled angina or arrhythmias), hypertension. Patient at risk of thromboembolism (e.g. prior thrombosis, concomitant oral contraceptive use or hormonal contraception). Ensure adequate hydration. Consider antiviral prophylaxis for patient with history of herpes zoster infection. Renal and hepatic impairment.
Adverse Reactions
Significant: Bone marrow suppression (e.g. thrombocytopenia, anaemia, lymphopenia, leukopenia, neutropenia), venous thromboembolism (e.g. deep vein thrombosis, pulmonary embolism), increased transaminases, hyperbilirubinemia, dyspnoea. Rarely, posterior reversible encephalopathy syndrome (PRES).
Blood and lymphatic system disorders: Febrile neutropenia.
Cardiac disorders: Atrial fibrillation, tachycardia, palpitations.
Ear and labyrinth disorders: Tinnitus.
Eye disorders: Cataract, blurred vision.
Gastrointestinal disorders: Gastroenteritis, vomiting, diarrhoea, constipation, abdominal pain, nausea, dyspepsia, oropharyngeal pain, toothache.
General disorders and administration site conditions: Hyperhidrosis, pyrexia, asthenia, fatigue, chills, pain, malaise.
Infections and infestations: Sepsis, viral infection (e.g. influenza, herpes zoster).
Investigations: Increased blood creatinine, decreased creatinine clearance.
Metabolism and nutrition disorders: Hypokalaemia, hyperglycaemia, decreased appetite, dehydration, hyperkalaemia, hypomagnesaemia, hyponatraemia, hyper/hypocalcaemia, hypophosphataemia, hyperuricaemia, hypoalbuminaemia, peripheral oedema.
Musculoskeletal and connective tissue disorders: Back pain, pain in extremity, muscle spasms, musculoskeletal pain, muscular weakness.
Nervous system disorders: Dizziness, peripheral neuropathy, headache, paraesthesia, hypoaesthesia.
Psychiatric disorders: Insomnia, anxiety, confusional state.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Pneumonia, respiratory tract infection, bronchitis, nasopharyngitis, rhinitis, lung infection, cough, dysphonia, wheezing.
Skin and subcutaneous tissue disorders: Rash, pruritus, erythema.
Potentially Fatal: New onset or worsening cardiac failure (e.g. congestive heart failure, pulmonary oedema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischaemia, MI, cardiac arrest, acute respiratory distress syndrome, acute respiratory failure, acute diffuse infiltrative pulmonary disease (e.g. pneumonitis, interstitial lung disease), hypertension (e.g. hypertensive crisis, hypertensive emergency); renal toxicity (e.g. renal insufficiency, renal failure, acute renal failure), tumour lysis syndrome, infusion reactions (e.g. fever, chills, facial oedema, angina, hypotension, flushing, myalgia, arthralgia), haemorrhage (e.g. gastrointestinal, pulmonary, intracranial, epistaxis), thrombotic microangiopathy (e.g. thrombocytopenic thrombotic purpura, haemolytic uraemic syndrome). Rarely, hepatic failure.
IV/Parenteral: D
Patient Counseling Information
This drug may cause fatigue, dizziness, fainting, blurred vision, somnolence and low blood pressure, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor serum K, liver enzymes and bilirubin, renal and pulmonary function; CBC with differential and platelets, blood pressure, haemorrhage. Monitor for signs and symptoms of cardiac failure or ischaemia, volume overload.
Drug Interactions
Carfilzomib at low concentrations may inhibit the efflux transport of P-gp substrate (e.g. digoxin, colchicine). Oral contraceptives may increase risk of thrombosis.
Potentially Fatal: Increased toxicity with melphalan and prednisone.
Action
Description: Carfilzomib is a proteasome inhibitor that selectively and irreversibly binds to the N-terminal threonine-containing active sites of 20S proteasome, a core unit within the 26s proteasome, resulting to disruption of tumour cell turnover and apoptosis.
Pharmacokinetics:
Distribution: Extensively penetrates all tissues except the brain. Volume of distribution: 28 L. Plasma protein binding: 97%.
Metabolism: Rapidly and extensively metabolised via peptidase cleavage and epoxide hydrolysis and minimal metabolism via CYP450-mediated mechanisms.
Excretion: Via urine (approx 25% as metabolites; <1% as unchanged drug), faeces (<1% as unchanged drug). Elimination half-life: ≤1 hour (≥15 mg/m2 doses).
Chemical Structure

Chemical Structure Image
Carfilzomib

Source: National Center for Biotechnology Information. PubChem Database. Carfilzomib, CID=11556711, https://pubchem.ncbi.nlm.nih.gov/compound/Carfilzomib (accessed on Jan. 21, 2020)

Storage
Store between 2-8°C. Do not freeze. Protect from light. Reconstituted solution: Store at 25°C for 4 hours or between 2-8°C for 24 hours.
ATC Classification
L01XX45 - carfilzomib ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Carfilzomib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 30/09/2019.

Buckingham R (ed). Carfilzomib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2019.

Joint Formulary Committee. Carfilzomib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2019.

Kyprolis (Onyx Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 30/09/2019.

Disclaimer: This information is independently developed by MIMS based on Carfilzomib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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