Difference between revisions of "Carfilzomib (Kyprolis)"

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'''FDA approved 7/20/2012'''.  Also known as CFZ or PR-171.
 
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==General information==
 
==General information==
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Class/mechanism: Second-generation proteasome inhibitor that interferes with degradation of ubiquitinated proteins by binding irreversibly to the 20S proteasome, which is the proteolytic core particle inside the 26S proteasome. This disrupts normal homeostatic mechanisms, leading to impaired tumor proliferation, apoptosis/cell death.<ref name="insert">[http://kyprolis.com/Content/pdf/PrescribingInformation.pdf Carfilzomib (Kyprolis) package insert]</ref><ref>[[Media:Carfilzomib.pdf|Carfilzomib (Kyprolis) package insert (locally hosted backup)]]</ref><ref>[http://kyprolis.com Kyprolis manufacturer's website]</ref><ref>[http://kyprolis.com/Content/pdf/PressRelease.pdf Kyprolis 7/20/2012 FDA approval press release]</ref><ref>[http://www.onyx.com/clinical-development/carfilzomib Carfilzomib (Kyprolis) manufacturer's clinical development website]</ref>
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Class/mechanism: Second-generation proteasome inhibitor that interferes with degradation of ubiquitinated proteins by binding irreversibly to the 20S proteasome, which is the proteolytic core particle inside the 26S proteasome. This disrupts normal homeostatic mechanisms, leading to impaired tumor proliferation, apoptosis/cell death.<ref name="insert">[http://pi.amgen.com/united_states/kyprolis/kyprolis_pi.pdf Carfilzomib (Kyprolis) package insert]</ref><ref>[[:File:Carfilzomib.pdf|Carfilzomib (Kyprolis) package insert (locally hosted backup)]]</ref><ref>[http://kyprolis.com Kyprolis manufacturer's website]</ref><ref>[http://kyprolis.com/Content/pdf/PressRelease.pdf Kyprolis 7/20/2012 FDA approval press release]</ref><ref>[http://www.onyx.com/clinical-development/carfilzomib Carfilzomib (Kyprolis) manufacturer's clinical development website]</ref>
  
 
Route: IV
 
Route: IV
 
<br>Extravasation: no information
 
<br>Extravasation: no information
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J code: J9999 (not otherwise classified, antineoplastic drug), J3490 (unclassified drugs)
 
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<br>HCPCS code: C9399 (unclassified drugs and biologicals)
 
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<br>CPT code: 96409 (chemotherapy administration, push technique, single or initial substance)
 
 
<br>NDC: NDC 76075-101-01; NDC 76075-0101-01
 
<br>NDC: NDC 76075-101-01; NDC 76075-0101-01
  
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For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://reference.medscape.com/drug/kyprolis-carfilzomib-999762 Medscape], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>
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For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, [https://online.lexi.com/lco/action/login UpToDate Lexidrug], [http://reference.medscape.com/drug/kyprolis-carfilzomib-999762 Medscape], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>
  
 
==Diseases for which it is used==
 
==Diseases for which it is used==
 
*[[Multiple myeloma]]
 
*[[Multiple myeloma]]
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*[[Waldenström macroglobulinemia]]
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==Clinical trials==
 
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*[http://clinicaltrials.gov/ct2/show/NCT00530816 Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma - PX-171-004]<ref>Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, Belch A, Matous JV, Lee P, Rosen P, Sebag M, Vesole DH, Kunkel LA, Wear SM, Wong AF, Orlowski RZ, Siegel DS. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012 Jun 14;119(24):5661-70. Epub 2012 May 3. [http://bloodjournal.hematologylibrary.org/content/119/24/5661.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22555973 PubMed]</ref>
 
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*[http://clinicaltrials.gov/ct2/show/NCT01080391 Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma (ASPIRE)]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01302392 A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma (FOCUS)]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01029054 Carfilzomib and Lenalidomide With Dexamethasone Combination in Newly Diagnosed, Previously Untreated Multiple Myeloma]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01365559 Study of Carfilzomib for Multiple Myeloma Patients Who Are Relapsed/Refractory to Bortezomib-containing Treatments]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01137747 Carfilzomib in Patients With Relapsed Acute Myeloid or Acute Lymphoblastic Leukemia (AML ALL)]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01568866 Phase 3 Study With Carfilzomib and Dexamethasone Versus Velcade and Dexamethasone for Relapsed Multiple Myeloma Patients (ENDEAVOR)]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01365559 Study of Carfilzomib for Multiple Myeloma Patients Who Are Relapsed/Refractory to Bortezomib-containing Treatments]
 
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*[http://clinicaltrials.gov/ct2/show/NCT01246063 Carfilzomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Relapsed or Refractory Multiple Myeloma]
 
  
 
==Patient drug information==
 
==Patient drug information==
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*Brief patient counseling information is available on [http://kyprolis.com/Content/pdf/PrescribingInformation.pdf#page=21 pages 21-22 of the Carfilzomib (Kyprolis) package insert].<ref name="insert"></ref>
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*Brief patient counseling information is available in the [http://pi.amgen.com/united_states/kyprolis/kyprolis_pi.pdf Carfilzomib (Kyprolis) package insert].<ref name="insert"></ref>
 +
*[https://chemocare.com/druginfo/carfilzomib.aspx Carfilzomib (Kyprolis) patient drug information (Chemocare)]<ref>[https://chemocare.com/druginfo/carfilzomib.aspx Carfilzomib (Kyprolis) patient drug information (Chemocare)]</ref>
 
*[http://www.uptodate.com/contents/carfilzomib-patient-drug-information Carfilzomib (Kyprolis) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/carfilzomib-patient-drug-information Carfilzomib (Kyprolis) patient drug information (UpToDate)]</ref>
 
*[http://www.uptodate.com/contents/carfilzomib-patient-drug-information Carfilzomib (Kyprolis) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/carfilzomib-patient-drug-information Carfilzomib (Kyprolis) patient drug information (UpToDate)]</ref>
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 +
==History of changes in FDA indication==
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*2012-07-20: Received accelerated approval for the treatment of patients with [[Multiple myeloma|multiple myeloma]] who have received at least two prior therapies including [[Bortezomib (Velcade)|bortezomib]] and an [[:Category:Immunomodulatory_drugs_(IMiDs)|immunomodulatory agent]] and have demonstrated disease progression on or within 60 days of completion of the last therapy. ''(Based on PX-171-003-A1)''
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*2015-07-24: Accelerated approval in combination with [[Lenalidomide (Revlimid)|lenalidomide]] and [[Dexamethasone (Decadron)|dexamethasone]] for the treatment of patients with relapsed [[multiple myeloma]] who have received one to three prior lines of therapy. ''(Based on ASPIRE)''
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*2016-01-21: Full approval in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory [[multiple myeloma]] who have received one to three lines of therapy. ''(Based on ENDEAVOR and ARROW<sub>MM</sub>)''
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*2016-01-21: Full approval as a single agent for the treatment of patients with relapsed or refractory [[multiple myeloma]] who have received one or more lines of therapy. ''(Based on PX-171-004 bortezomib-naive and PX-171-007)''
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*2020-08-20: Approved in combination with [[Daratumumab (Darzalex)|daratumumab]] and [[Dexamethasone (Decadron)|dexamethasone]] for adult patients with relapsed or refractory [[multiple myeloma]] who have received one to three lines of therapy. ''(Based on CANDOR and EQUULEUS<sub>cfz</sub>)''
 +
==History of changes in EMA indication==
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*2015-11-19: Initial authorization as Kyprolis in combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with [[multiple myeloma]] who have received at least one prior therapy. ''(Based on ASPIRE)''
 +
*2016-06-29: Extension of Indication to include new indication for Kyprolis to be used with either lenalidomide and dexamethasone or dexamethasone alone for the treatment of adult patients with [[multiple myeloma]] who have received at least one prior therapy.
 +
*2020-12-17: Extension of existing indication to include combination of Kyprolis with daratumumab and dexamethasone.
 +
 +
==History of changes in Health Canada indication==
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*2016-01-15: Initial notice of compliance
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==History of changes in PMDA indication==
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*2016-07-04: New approval for the treatment of relapsed or refractory [[multiple myeloma]].
 +
==Post-marketing concerns==
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*2015-01: New safety information concerning posterior reversible encephalopathy syndrome (PRES), based on several case reports<ref>[https://doi.org/10.1200/JCO.2013.49.6166 Xuemei Cai and Shamik Bhattacharyya et al. 2014]</ref><ref>[http://austinpublishinggroup.com/hematology/download.php?file=fulltext/hematology-v2-id1018.pdf James Pauff et al. 2015]</ref>.
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==Also known as==
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*'''Code name:''' PR-171
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*'''Generic name:''' CFZ
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*'''Brand names:''' Carfilnat, Kyprolis
  
 
==References==
 
==References==
 
<references/>
 
<references/>
  
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[[Category:Drug index]]
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[[Category:Drugs]]
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[[Category:Chemotherapy]]
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[[Category:Intravenous medications]]
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[[Category:Proteasome inhibitors]]
 
[[Category:Proteasome inhibitors]]
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[[Category:Multiple myeloma medications]]
 
[[Category:Multiple myeloma medications]]
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[[Category:Drugs FDA approved in 2012]]
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[[Category:Waldenström macroglobulinemia medications]]
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[[Category:FDA approved in 2012]]
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[[Category:EMA approved in 2015]]
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[[Category:Health Canada approved in 2016]]
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[[Category:PMDA approved in 2016]]

Latest revision as of 01:50, 29 June 2024

General information

Class/mechanism: Second-generation proteasome inhibitor that interferes with degradation of ubiquitinated proteins by binding irreversibly to the 20S proteasome, which is the proteolytic core particle inside the 26S proteasome. This disrupts normal homeostatic mechanisms, leading to impaired tumor proliferation, apoptosis/cell death.[1][2][3][4][5]

Route: IV
Extravasation: no information
NDC: NDC 76075-101-01; NDC 76075-0101-01

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, UpToDate Lexidrug, Medscape, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Diseases for which it is used

Patient drug information

History of changes in FDA indication

  • 2012-07-20: Received accelerated approval for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. (Based on PX-171-003-A1)
  • 2015-07-24: Accelerated approval in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed multiple myeloma who have received one to three prior lines of therapy. (Based on ASPIRE)
  • 2016-01-21: Full approval in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. (Based on ENDEAVOR and ARROWMM)
  • 2016-01-21: Full approval as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. (Based on PX-171-004 bortezomib-naive and PX-171-007)
  • 2020-08-20: Approved in combination with daratumumab and dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. (Based on CANDOR and EQUULEUScfz)

History of changes in EMA indication

  • 2015-11-19: Initial authorization as Kyprolis in combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. (Based on ASPIRE)
  • 2016-06-29: Extension of Indication to include new indication for Kyprolis to be used with either lenalidomide and dexamethasone or dexamethasone alone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
  • 2020-12-17: Extension of existing indication to include combination of Kyprolis with daratumumab and dexamethasone.

History of changes in Health Canada indication

  • 2016-01-15: Initial notice of compliance

History of changes in PMDA indication

  • 2016-07-04: New approval for the treatment of relapsed or refractory multiple myeloma.

Post-marketing concerns

  • 2015-01: New safety information concerning posterior reversible encephalopathy syndrome (PRES), based on several case reports[8][9].

Also known as

  • Code name: PR-171
  • Generic name: CFZ
  • Brand names: Carfilnat, Kyprolis

References

  1. ↑ 1.0 1.1 1.2 Carfilzomib (Kyprolis) package insert
  2. ↑ Carfilzomib (Kyprolis) package insert (locally hosted backup)
  3. ↑ Kyprolis manufacturer's website
  4. ↑ Kyprolis 7/20/2012 FDA approval press release
  5. ↑ Carfilzomib (Kyprolis) manufacturer's clinical development website
  6. ↑ Carfilzomib (Kyprolis) patient drug information (Chemocare)
  7. ↑ Carfilzomib (Kyprolis) patient drug information (UpToDate)
  8. ↑ Xuemei Cai and Shamik Bhattacharyya et al. 2014
  9. ↑ James Pauff et al. 2015
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