Difference between revisions of "Panobinostat (Farydak)"

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'''Note: this drug has been withdrawn from the US market but is still available in the EU and UK.'''
 
==General information==
 
==General information==
−
Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi.  Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes.  This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.<ref name=insert>[http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf Panobinostat (Farydak) package insert]</ref><ref>[[Media:Panobinostat.pdf|Panobinostat (Farydak) package insert, locally hosted backup]]</ref><ref>[http://www.novartisoncology.com/ct/pipelineDetails?compound=LBH589&diseaseAcr=MM Novartis's information about panobinostat]</ref><ref>Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089964/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21242994 PubMed]</ref><ref>Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. [http://mct.aacrjournals.org/content/8/8/2221.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19671764 PubMed]</ref>
+
Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi.  Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes.  This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.<ref name=insert>[https://us.farydak.com/assets/pdf/Farydak-SBI-USPI-201909.pdf Panobinostat (Farydak) package insert]</ref><ref>[[:File:Panobinostat.pdf|Panobinostat (Farydak) package insert, locally hosted backup]]</ref><ref>[http://www.novartisoncology.com/ct/pipelineDetails?compound=LBH589&diseaseAcr=MM Novartis's information about panobinostat]</ref><ref>Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089964/ link to original article] [https://pubmed.ncbi.nlm.nih.gov/21242994/ PubMed]</ref><ref>Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. [http://mct.aacrjournals.org/content/8/8/2221.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/19671764/ PubMed]</ref>
 
<br>Route: PO
 
<br>Route: PO
 
<br>Extravasation: n/a
 
<br>Extravasation: n/a
  
−
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://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>
+
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://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==
−
*[[Acute myeloid leukemia]]
+
*[[Diffuse large B-cell lymphoma]]
−
*[[Hodgkin lymphoma]]
 
 
*[[Multiple myeloma]]
 
*[[Multiple myeloma]]
−
*[[Peripheral T-cell lymphoma]]
+
 
−
*[[Waldenström macroglobulinemia]]
+
==Diseases for which it was used==
 +
*[[Acute myeloid leukemia - historical|Acute myeloid leukemia]]
 +
*[[Classical Hodgkin lymphoma - historical|Hodgkin lymphoma]]
 +
*[[Peripheral T-cell lymphoma - historical|Peripheral T-cell lymphoma]]
 +
*[[Waldenström macroglobulinemia - historical|Waldenström macroglobulinemia]]
  
 
==Monitoring recommendations==
 
==Monitoring recommendations==
−
Panobinostant has an [http://www.farydak-rems.com/ informational REMS] in place for severe diarrhea and cardiac toxicities.
+
Panobinostant had an [http://www.farydak-rems.com/ informational REMS] in place for severe diarrhea and cardiac toxicities.
 
*Refer to the [http://www.farydak-rems.com/assets/pdf/FDK-1110411_820941_M04R_FAK_REMS_FactSheet.pdf Factsheet] for detailed diarrhea management information.
 
*Refer to the [http://www.farydak-rems.com/assets/pdf/FDK-1110411_820941_M04R_FAK_REMS_FactSheet.pdf Factsheet] for detailed diarrhea management information.
 
*Per the REMS, do not start panobinostat if patient has any of the following:
 
*Per the REMS, do not start panobinostat if patient has any of the following:
 
**Recent myocardial infarction
 
**Recent myocardial infarction
 
**Unstable angina
 
**Unstable angina
−
**QTcF ≥ 450 msec
+
**QTcF any longer than 450 msec
 
**Clinically significant ST-segment or T-wave abnormalities
 
**Clinically significant ST-segment or T-wave abnormalities
  
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==History of changes in FDA indication==
 
==History of changes in FDA indication==
−
*2/23/2015: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435296.htm FDA accelerated approval] "for the treatment of patients with [[Multiple myeloma|multiple myeloma]] who have received at least 2 prior regimens, including [[Bortezomib (Velcade)|bortezomib]] and an [[:Category:Immunomodulatory_drugs_(IMiDs)|immunomodulatory agent]]."
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===[[Multiple myeloma]] - '''WITHDRAWN'''===
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*2015-02-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435296.htm FDA accelerated approval] for the treatment of patients with [[Multiple myeloma|multiple myeloma]] who have received at least 2 prior regimens, including [[Bortezomib (Velcade)|bortezomib]] and an [[:Category:Immunomodulatory_drugs_(IMiDs)|immunomodulatory agent]]. ''(Based on PANORAMA 1)''
 +
**2022-03-24: Accelerated approval for the treatment of patients with [[Multiple myeloma|multiple myeloma]] who have received at least 2 prior regimens, including [[Bortezomib (Velcade)|bortezomib]] and an [[:Category:Immunomodulatory_drugs_(IMiDs)|immunomodulatory agent]] withdrawn at the request of the manufacturer. ''(No supporting studies are cited)''
  
 +
==History of changes in EMA indication==
 +
*2015-08-28: Initial marketing authorization as Farydak.
 +
*Uncertain date: Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory [[multiple myeloma]] who have received at least two prior regimens including bortezomib and an immunomodulatory agent.
 +
==History of changes in PMDA indication==
 +
*2015-07-03: Initial approval for the treatment of relapsed or refractory [[multiple myeloma]].
 
==Also known as==
 
==Also known as==
−
*'''Code name:''' LBH589
+
*'''Code name:''' LBH-589
 +
*'''Generic name:''' panobinostat lactate anhydrous
 
*'''Brand names:''' Faridak, Farydak
 
*'''Brand names:''' Faridak, Farydak
  
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<references/>
 
<references/>
  
−
[[Category:Drug index]]
+
[[Category:Drugs]]
 
[[Category:Oral medications]]
 
[[Category:Oral medications]]
 
[[Category:HDAC inhibitors]]
 
[[Category:HDAC inhibitors]]
  
−
[[Category:Acute myeloid leukemia medications]]
+
[[Category:Diffuse large B-cell lymphoma medications]]
−
[[Category:Hodgkin lymphoma medications]]
 
 
[[Category:Multiple myeloma medications]]
 
[[Category:Multiple myeloma medications]]
−
[[Category:Peripheral T-cell lymphoma medications]]
+
 
−
[[Category:Waldenström macroglobulinemia medications]]
+
[[Category:Acute myeloid leukemia medications (historic)]]
 +
[[Category:Classical Hodgkin lymphoma medications (historic)]]
 +
[[Category:Peripheral T-cell lymphoma medications (historic)]]
 +
[[Category:Waldenström macroglobulinemia medications (historic)]]
  
 
[[Category:REMS program]]
 
[[Category:REMS program]]
−
[[Category:Drugs FDA approved in 2015]]
+
[[Category:EMA approved in 2015]]
−
[[Category:FDA approved drugs]]
+
[[Category:FDA approved in 2015]]
−
[[Category:PMDA approved drugs]]
+
 
 +
[[Category:FDA withdrawn in 2022]]
 +
[[Category:EMA approved in 2015]]
 +
[[Category:PMDA approved in 2015]]

Latest revision as of 11:44, 9 April 2024

Note: this drug has been withdrawn from the US market but is still available in the EU and UK.

General information

Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi. Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes. This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.[1][2][3][4][5]
Route: PO
Extravasation: n/a

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, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Diseases for which it is used

Diseases for which it was used

Monitoring recommendations

Panobinostant had an informational REMS in place for severe diarrhea and cardiac toxicities.

  • Refer to the Factsheet for detailed diarrhea management information.
  • Per the REMS, do not start panobinostat if patient has any of the following:
    • Recent myocardial infarction
    • Unstable angina
    • QTcF any longer than 450 msec
    • Clinically significant ST-segment or T-wave abnormalities

Patient drug information

History of changes in FDA indication

Multiple myeloma - WITHDRAWN

History of changes in EMA indication

  • 2015-08-28: Initial marketing authorization as Farydak.
  • Uncertain date: Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent.

History of changes in PMDA indication

  • 2015-07-03: Initial approval for the treatment of relapsed or refractory multiple myeloma.

Also known as

  • Code name: LBH-589
  • Generic name: panobinostat lactate anhydrous
  • Brand names: Faridak, Farydak

References

  1. ↑ 1.0 1.1 1.2 Panobinostat (Farydak) package insert
  2. ↑ Panobinostat (Farydak) package insert, locally hosted backup
  3. ↑ Novartis's information about panobinostat
  4. ↑ Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. link to original article PubMed
  5. ↑ Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. link to original article PubMed
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