Panobinostat: Difference between revisions

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{{Drugbox
{{DrugProjectFormSinglePage
| Verifiedfields = changed
|authorTag={{MN}}
| Watchedfields = changed
|genericName=Panobinostat
| verifiedrevid = 455315413
|aOrAn=a
| IUPAC_name = (2''E'')-''N''-hydroxy-3-[4-({[2-(2-methyl-1''H''-indol-3-yl)ethyl]amino}methyl)phenyl]acrylamide
|drugClass=[[histone]] deacetylase inhibitor
| image =Panobinostat structure.png
|indicationType=treatment
<!--Clinical data-->
|indication=patients with [[multiple myeloma]] (in combination with [[bortezomib]] and [[dexamethasone]]) who have received at least 2 prior regimens, including [[bortezomib]] and an [[immunomodulatory]] agent
| tradename = Farydak
|adverseReactions=[[diarrhea]], [[fatigue]], [[nausea]], peripheral [[edema]], decreased appetite, [[pyrexia]], and [[vomiting]] (≥20%)
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
|hasBlackBoxWarning=Yes
| pregnancy_US = <!-- A / B            / C / D / X -->
|blackBoxWarningTitle=<span style="color:#FF0000;">FATAL AND SERIOUS TOXICITIES: SEVERE DIARRHEA AND CARDIAC TOXICITIES</span>
| pregnancy_category =
|blackBoxWarningBody=<i><span style="color:#FF0000;">
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
Severe diarrhea occurred in 25% of FARYDAK treated patients. Monitor for symptoms, institute anti-diarrheal treatment, interrupt FARYDAK and then reduce dose or discontinue FARYDAK. (5.1)
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = Rx-only
| legal_status =  
| routes_of_administration = Oral


<!--Pharmacokinetic data-->
Severe and fatal cardiac ischemic events, severe [[arrhythmias]], and [[ECG]] changes have occurred in patients receiving FARYDAK. Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at baseline and periodically during treatment as clinically indicated.
| bioavailability = 21%<ref name="PackageInsert">[http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf Panobinostat Package Insert]</ref>
</span></i>
| protein_bound = 90%<ref name="PackageInsert" />
|fdaLIADAdult=
| metabolism = [[CYP3A]] (40%), [[CYP2D6]], [[CYP2C19]]<ref name="PackageInsert" />
======Indications======
| elimination_half-life = 37 hours<ref name="PackageInsert" />
FARYDAK, a [[histone]] deacetylase inhibitor, in combination with [[bortezomib]] and [[dexamethasone]], is indicated for the treatment of patients with [[multiple myeloma]] who have received at least 2 prior regimens, including [[bortezomib]] and an [[immunomodulatory]] agent. This indication is approved under accelerated approval based on progression free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
| excretion = Fecal (44–77%), renal (29–51%)<ref name="PackageInsert" />


<!--Identifiers-->
======Dosage======
| CAS_number_Ref = {{cascite|correct|??}}
:*Recommended Dosing
| CAS_number = 404950-80-7
::*The recommended starting dose of FARYDAK is 20 mg, taken orally once every other day for 3 doses per week in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles. Consider continuing treatment for an additional 8 cycles for patients with clinical benefit who do not experience unresolved severe or medically significant toxicity. The total duration of treatment may be up to 16 cycles (48 weeks). FARYDAK is administered in combination with [[bortezomib]] and [[dexamethasone]] as shown in Table 1 and Table 2.
| ATC_prefix = L01
| ATC_suffix = XX42
| ATC_supplemental =  
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 5294028
| PubChem = 6918837
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =  
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D10019
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9647FM7Y3Z


<!--Chemical data-->
::*The recommended dose of [[bortezomib]] is 1.3 mg/m2 given as an injection. The recommended dose of [[dexamethasone]] is 20 mg taken orally per scheduled day, on a full stomach.
| chemical_formula = 
 
| C=21 | H=23 | N=3 | O=2  
:*'''Table 1: Recommended Dosing Schedule of FARYDAK in Combination with Bortezomib and Dexamethasone During Cycles 1 to 8'''
| molecular_weight = 349.42622 g/mol
[[File:table1_pan.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
| smiles = O=C(NO)\C=C\c1ccc(cc1)CNCCc3c2ccccc2nc3C
<SMALL>FARYDAK: Panobinostat's Brand name</SMALL>
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
 
| StdInChI = 1S/C21H23N3O2/c1-15-18(19-4-2-3-5-20(19)23-15)12-13-22-14-17-8-6-16(7-9-17)10-11-21(25)24-26/h2-11,22-23,26H,12-14H2,1H3,(H,24,25)/b11-10+
:*'''Table 2: Recommended Dosing Schedule of FARYDAK in Combination with Bortezomib and Dexamethasone During Cycles 9 to 16'''
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
[[File:table2_pan.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
| StdInChIKey = FPOHNWQLNRZRFC-ZHACJKMWSA-N
<SMALL>FARYDAK: Panobinostat's Brand name</SMALL>
}}
 
__Notoc__
:*Dose Adjustments and Modifications for Toxicity
{{SI}}
::*Dose and/or schedule modification of FARYDAK may be required based on [[toxicity]]. Management of adverse drug reactions may require treatment interruption and/or dose reductions. If dose reduction is required, the dose of FARYDAK should be reduced in increments of 5 mg (i.e., from 20 mg to 15 mg, or from 15 mg to 10 mg). If the dosing of FARYDAK is reduced below 10 mg given 3 times per week, discontinue FARYDAK. Keep the same treatment schedule (3-week treatment cycle) when reducing dose. The table also lists [[Bortezomib]] (BTZ) dose modification procedures from the clinical trials.
{{CMG}}
 
:*'''Table 3: Dose Modifications for Most Common Toxicities'''
[[File:table3_pan.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
<SMALL>FARYDAK: Panobinostat's Brand name</SMALL>
 
::*'''[[Myelosuppression]]'''
 
:::*Interrupt or reduce the dose of FARYDAK in patients who have [[thrombocytopenia]], [[neutropenia]] or [[anemia]] according to instructions in Table 3. For patients with severe thrombocytopenia, consider [[platelet]] transfusions. Discontinue FARYDAK treatment if thrombocytopenia does not improve despite the recommended treatment modifications or if repeated platelet transfusions are required.
 
:::*In the event of Grade 3 or 4 [[neutropenia]], consider dose reduction and/or the use of [[growth factors]] (e.g., [[G-CSF]]). Discontinue FARYDAK if neutropenia does not improve despite dose modifications, [[colony-stimulating factors]], or in case of severe infection.
 
::*'''Gastrointestinal Toxicity'''
 
:::*Gastrointestinal toxicity is common in patients treated with FARYDAK. Patients who experience [[diarrhea]], [[nausea]], or [[vomiting]] may require treatment interruption or dose reduction (Table 3). At the first sign of [[abdominal cramping]], loose stools, or onset of diarrhea, patients should be treated with anti-diarrheal medication (e.g., [[loperamide]]). Consider and administer [[prophylactic]] [[anti-emetics]] as clinically indicated.
 
::*'''Other Adverse Drug Reactions'''
 
:::*For patients experiencing Grade 3/4 adverse drug reactions other than [[thrombocytopenia]], [[neutropenia]], or gastrointestinal toxicity, the recommendation is the following:
 
::::*CTC Grade 2 toxicity recurrence and CTC Grade 3 and 4 - omit the dose until recovery to CTC Grade 1 or less and restart treatment at a reduced dose
::::*CTC Grade 3 or 4 toxicity recurrence, a further dose reduction may be considered once the adverse events have resolved to CTC Grade 1 or less.
 
:*Dose Modifications for Use in Hepatic Impairment
 
::*Reduce the starting dose of FARYDAK to 15 mg in patients with mild hepatic impairment and 10 mg in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment. Monitor patients frequently for adverse events and adjust dose as needed for [[toxicity]].
 
:*Dose Modifications for Use with Strong [[CYP3A]] Inhibitors
 
::*Reduce the starting dose of FARYDAK to 10 mg when coadministered with strong CYP3A inhibitors (e.g., [[boceprevir]], [[clarithromycin]], [[conivaptan]], [[indinavir]], [[itraconazole]], [[ketoconazole]], [[lopinavir]]/[[ritonavir]]).
 
 
 
 
 
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Pimavanserin in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Pimavanserin in adult patients.
|fdaLIADPed=Safety and effectiveness have not been established in pediatric patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Pimavanserin in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Pimavanserin in pediatric patients.
|contraindications=
|warnings=
|clinicalTrials=
|postmarketing=
|drugInteractions=
|FDAPregCat=
|useInPregnancyFDA=
|useInLaborDelivery=
|useInNursing=
|useInPed=
|useInGeri=
|useInRenalImpair=
|useInHepaticImpair=
|useInReproPotential=
|useInImmunocomp=
|othersTitle=
|useInOthers=
|administration=
:*FARYDAK should be taken orally once on each scheduled day at about the same time, either with or without food
 
:*FARYDAK capsules should be swallowed whole with a cup of water. Do not open, crush, or chew the capsules


==Overview==
:*If a dose is missed it can be taken up to 12 hours after the specified dose time. If vomiting occurs the patient should not repeat the dose, but should take the next usual scheduled dose.


'''Panobinostat''' ('''LBH-589''', trade name '''Farydak''') is a drug developed by [[Novartis]] for the treatment of various cancers. It is a [[hydroxamic acid]]<ref name=Revill2007/> and acts as a non-selective [[histone deacetylase inhibitor]] (pan-HDAC inhibitor).<ref name=NBT2010>[http://www.nature.com/nbt/journal/v28/n12/fig_tab/nbt.1724_T3.html Table 3: Select epigenetic inhibitors in various stages of development] from {{cite doi|10.1038/nbt.1724}}</ref>
:*Counsel patients on the correct dosing schedule, technique of administration of FARYDAK, and when to take FARYDAK if dosing adjustments are made.


On 23 February 2015 it received FDA accelerated approval for use in patients with [[multiple myeloma]] who had received at least 2 previous treatments, including [[bortezomib]] and an [[Immunomodulatory drug|immunomodulatory agent]]."<ref>[http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435296.htm FDA.gov announcement about accelerated approval of panobinostat (Farydak)]</ref> after clinical trials.<ref>[http://hemonc.org/wiki/Multiple_myeloma#Bortezomib.2C_Dexamethasone.2C_Panobinostat Panobinostat chemotherapy regimen for multiple myeloma (MM wiki)]</ref>


==Clinical trials==
|monitoring=
{{As of|2012|8}}, it is being tested against [[Hodgkin's Lymphoma]], [[cutaneous T cell lymphoma]] (CTCL)<ref>{{ClinicalTrialsGov|NCT00425555|Study of Oral LBH589 in Adult Patients With Refractory Cutaneous T-Cell Lymphoma}}</ref> and other types of malignant disease in Phase III [[clinical trial]]s, against [[myelodysplastic syndromes]], [[breast cancer]] and [[prostate cancer]] in Phase II trials, and against [[chronic myelomonocytic leukemia]] (CMML) in a Phase I trial.<ref>[http://clinicaltrials.gov/search/intervention=lbh-589 ClinicalTrials.gov: LBH-589]</ref><ref name="pan">{{cite journal|last=Prince|first=HM|author2=M Bishton|year=2009|title=Panobinostat (LBH589): a novel pan-deacetylase inhibitor with activity in T cell lymphoma|journal=Hematology Meeting Reports|publisher=Peter MacCallum Cancer Centre and University of Melbourne|location=Parkville, Australia|volume=3|issue=1|pages=33–38|url=http://www.pagepress.org/journals/index.php/hmr/article/viewFile/526/606}}</ref>
Prior to the start of FARYDAK treatment and during treatment, monitoring should include:


{{As of |2014}} Panobinostat is being used in a Phase I/II clinical trial that aims at curing AIDS in patients on [[highly active antiretroviral therapy]] (HAART). In this technique, panobinostat is used to drive the HIV DNA out of the patient's DNA, in the expectation that the patient's immune system in combination with HAART will destroy it.<ref name="Jake Wallis Simons2013">{{cite news|last=Simons|first=J|title=Scientists on brink of HIV cure|publisher=The Telegraph|url=http://www.telegraph.co.uk/health/healthnews/10022664/Scientists-on-brink-of-HIV-cure.html|date=27 April 2013}}</ref><ref>{{ClinicalTrialsGov|NCT01680094|Safety and Effect of The HDAC Inhibitor Panobinostat on HIV-1 Expression in Patients on Suppressive HAART (CLEAR)}}</ref> <ref>{{cite doi|10.1016/S2352-3018(14)70014-1}}</ref>
:*'''[[Complete Blood Count]] (CBC):''' Obtain a CBC before initiating treatment. Verify that the baseline [[platelet]] count is at least 100 x 109/L and the baseline absolute [[neutrophil]] count (ANC) is at least 1.5 x 109/L. Monitor the CBC weekly (or more often as clinically indicated) during treatment.
:*'''[[ECG]]''': Perform an ECG prior to the start of therapy and repeat periodically during treatment as clinically indicated. Verify that the QTcF is less than 450 msec prior to initiation of treatment with FARYDAK. If during treatment with FARYDAK, the QTcF increases to ≥480 msec, interrupt treatment. Correct any [[electrolyte]] abnormalities. If [[QT]] prolongation does not resolve, permanently discontinue treatment with FARYDAK. During the clinical trial, ECGs were performed at baseline and prior to initiation of each cycle for the first 8 cycles.
:*'''Serum [[Electrolytes]]:''' Obtain electrolytes, including [[potassium]] and [[magnesium]], at baseline and monitor during therapy. Correct abnormal electrolyte values before treatment. During the trial, monitoring was conducted prior to the start of each cycle, at Day 11 of cycles 1 to 8, and at the start of each cycle for cycles 9 to 16.


==Preclinical studies==
For additional information please refer to the [[bortezomib]] and [[dexamethasone]] prescribing information.
Panobinostat has been found to synergistically act with [[sirolimus]] to kill pancreatic cancer cells in the laboratory in a [[Mayo Clinic]] study.  In the study, investigators found that this combination destroyed up to 65 percent of cultured pancreatic tumor cells. The finding is significant because the three cell lines studied were all resistant to the effects of chemotherapy – as are many pancreatic tumors.<ref>[http://www.mayoclinic.org/news2009-rst/5245.html Mayo Clinic Researchers Formulate Treatment Combination Lethal To Pancreatic Cancer Cells]</ref>


Panobinostat has also been found to significantly increase ''[[in vitro]]'' the [[survival of motor neuron]] (SMN) protein levels in cells of patients suffering from [[spinal muscular atrophy]].<ref>{{cite journal|journal=Human Molecular Genetics|year=2009|volume=18|issue=19|pages=3645–3658|last=Garbes|first=L|author2=Riessland, M |author3=Hölker, I |author4=Heller, R |author5=Hauke, J |author6=Tränkle, Ch |author7=Coras, R |author8=Blümcke, I |author9=Hahnen, E |author10= Wirth, B |url=http://hmg.oxfordjournals.org/cgi/content/abstract/ddp313|title=LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate|doi=10.1093/hmg/ddp313|pmid=19584083}}</ref>
|overdose=
|drugBox={{Drugbox2
}}


Panobinostat was able to selectively target [[triple negative breast cancer]] (TNBC) cells by inducing hyperacetylation and cell cycle arrest at the [[G2-M DNA damage checkpoint]]; partially reversing the morphological changes characteristic of breast cancer cells.<ref>{{cite journal|last=Tate|first=CR|author2=Rhodes, LV |author3=Segar, HC |author4=Driver, JL |author5=Pounder, FN |author6=Burow, ME |author7= Collins-Burow, BM |year=2012|title=Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat
|mechAction=
|journal=Breast Cancer Research|volume=14|issue=3|url=http://breast-cancer-research.com/content/14/3/R79}}</ref>
|structure=
|PD=
|PK=
|nonClinToxic=======[[Carcinogenesis]], [[Mutagenesis]], Impairment of [[Fertility]]======
|clinicalStudies=
|howSupplied=
Capsules: 10 mg, 15 mg, and 20 mg panobinostat (equivalent to 12.58 mg, 18.86 mg, and 25.15 mg respectively of panobinostat lactate)


Panobinostat, along with other HDAC inhibitors, is also being studied for potential to induce virus HIV-1 expression in latently infected cells and disrupt latency. These resting cells are not recognized by the immune system as harboring the virus and do not respond to antiretroviral drugs.<ref>TA Rasmussen, et al. Comparison of HDAC inhibitors in clinical development: Effect on HIV production in latently infected cells and T-cell activation. Human Vaccines & Immunotherapeutics 9:5, 1-9, May 2013.</ref>
10 mg: Size #3 light green opaque capsule, radial markings on cap with black ink “LBH 10 mg” and two radial bands with black ink on body, containing white to almost white powder.


==Mechanism of action==
15 mg: Size #1 orange opaque capsule, radial markings on cap with black ink “LBH 15 mg” and two radial bands with black ink on body, containing white to almost white powder.
Panobinostat inhibits multiple [[histone deacetylase]] enzymes, a mechanism leading to [[apoptosis]] of malignant cells via multiple pathways.<ref name=Revill2007>{{cite journal|last=Revill|first=P|author2=Mealy, N |author3=Serradell, N |author4=Bolos, J |author5= Rosa, E |year=2007|title=Panobinostat|journal=Drugs of the Future|volume=32|issue=4|pages=315|issn=0377-8282|url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1094476&p_IsPs=N|doi=10.1358/dof.2007.032.04.1094476}}</ref>


==References==
20 mg: Size #1 red opaque capsule, radial markings on cap with black ink “LBH 20 mg” and two radial bands with black ink on body, containing white to almost white powder.
{{Reflist|35em}}


{{Intracellular chemotherapeutic agents}}


[[Category:Indoles]]
|storage=
[[Category:Hydroxamic acids]]
|packLabel=[[File:pima.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[Category:Histone deacetylase inhibitors]]
|fdaPatientInfo=
[[Category:Experimental cancer drugs]]
|brandNames=
}}

Revision as of 14:30, 8 February 2017

Panobinostat
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Martin Nino [2]

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Black Box Warning

FATAL AND SERIOUS TOXICITIES: SEVERE DIARRHEA AND CARDIAC TOXICITIES
See full prescribing information for complete Boxed Warning.

Severe diarrhea occurred in 25% of FARYDAK treated patients. Monitor for symptoms, institute anti-diarrheal treatment, interrupt FARYDAK and then reduce dose or discontinue FARYDAK. (5.1)

Severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes have occurred in patients receiving FARYDAK. Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at baseline and periodically during treatment as clinically indicated.

Overview

Panobinostat is a histone deacetylase inhibitor that is FDA approved for the treatment of patients with multiple myeloma (in combination with bortezomib and dexamethasone) who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent. There is a Black Box Warning for this drug as shown here. Common adverse reactions include diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting (≥20%).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

FARYDAK, a histone deacetylase inhibitor, in combination with bortezomib and dexamethasone, is indicated for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent. This indication is approved under accelerated approval based on progression free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Dosage
  • Recommended Dosing
  • The recommended starting dose of FARYDAK is 20 mg, taken orally once every other day for 3 doses per week in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles. Consider continuing treatment for an additional 8 cycles for patients with clinical benefit who do not experience unresolved severe or medically significant toxicity. The total duration of treatment may be up to 16 cycles (48 weeks). FARYDAK is administered in combination with bortezomib and dexamethasone as shown in Table 1 and Table 2.
  • The recommended dose of bortezomib is 1.3 mg/m2 given as an injection. The recommended dose of dexamethasone is 20 mg taken orally per scheduled day, on a full stomach.
  • Table 1: Recommended Dosing Schedule of FARYDAK in Combination with Bortezomib and Dexamethasone During Cycles 1 to 8
This image is provided by the National Library of Medicine.

FARYDAK: Panobinostat's Brand name

  • Table 2: Recommended Dosing Schedule of FARYDAK in Combination with Bortezomib and Dexamethasone During Cycles 9 to 16
This image is provided by the National Library of Medicine.

FARYDAK: Panobinostat's Brand name

  • Dose Adjustments and Modifications for Toxicity
  • Dose and/or schedule modification of FARYDAK may be required based on toxicity. Management of adverse drug reactions may require treatment interruption and/or dose reductions. If dose reduction is required, the dose of FARYDAK should be reduced in increments of 5 mg (i.e., from 20 mg to 15 mg, or from 15 mg to 10 mg). If the dosing of FARYDAK is reduced below 10 mg given 3 times per week, discontinue FARYDAK. Keep the same treatment schedule (3-week treatment cycle) when reducing dose. The table also lists Bortezomib (BTZ) dose modification procedures from the clinical trials.
  • Table 3: Dose Modifications for Most Common Toxicities
This image is provided by the National Library of Medicine.

FARYDAK: Panobinostat's Brand name

  • Interrupt or reduce the dose of FARYDAK in patients who have thrombocytopenia, neutropenia or anemia according to instructions in Table 3. For patients with severe thrombocytopenia, consider platelet transfusions. Discontinue FARYDAK treatment if thrombocytopenia does not improve despite the recommended treatment modifications or if repeated platelet transfusions are required.
  • Gastrointestinal Toxicity
  • Gastrointestinal toxicity is common in patients treated with FARYDAK. Patients who experience diarrhea, nausea, or vomiting may require treatment interruption or dose reduction (Table 3). At the first sign of abdominal cramping, loose stools, or onset of diarrhea, patients should be treated with anti-diarrheal medication (e.g., loperamide). Consider and administer prophylactic anti-emetics as clinically indicated.
  • Other Adverse Drug Reactions
  • For patients experiencing Grade 3/4 adverse drug reactions other than thrombocytopenia, neutropenia, or gastrointestinal toxicity, the recommendation is the following:
  • CTC Grade 2 toxicity recurrence and CTC Grade 3 and 4 - omit the dose until recovery to CTC Grade 1 or less and restart treatment at a reduced dose
  • CTC Grade 3 or 4 toxicity recurrence, a further dose reduction may be considered once the adverse events have resolved to CTC Grade 1 or less.
  • Dose Modifications for Use in Hepatic Impairment
  • Reduce the starting dose of FARYDAK to 15 mg in patients with mild hepatic impairment and 10 mg in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment. Monitor patients frequently for adverse events and adjust dose as needed for toxicity.
  • Dose Modifications for Use with Strong CYP3A Inhibitors

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness have not been established in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in pediatric patients.

Contraindications

There is limited information regarding Panobinostat Contraindications in the drug label.

Warnings

FATAL AND SERIOUS TOXICITIES: SEVERE DIARRHEA AND CARDIAC TOXICITIES
See full prescribing information for complete Boxed Warning.

Severe diarrhea occurred in 25% of FARYDAK treated patients. Monitor for symptoms, institute anti-diarrheal treatment, interrupt FARYDAK and then reduce dose or discontinue FARYDAK. (5.1)

Severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes have occurred in patients receiving FARYDAK. Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at baseline and periodically during treatment as clinically indicated.

There is limited information regarding Panobinostat Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Panobinostat Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Panobinostat Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Panobinostat Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Panobinostat in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Panobinostat in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Panobinostat during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Panobinostat in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Panobinostat in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Panobinostat in geriatric settings.

Gender

There is no FDA guidance on the use of Panobinostat with respect to specific gender populations.

Race

There is no FDA guidance on the use of Panobinostat with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Panobinostat in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Panobinostat in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Panobinostat in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Panobinostat in patients who are immunocompromised.

Administration and Monitoring

Administration

  • FARYDAK should be taken orally once on each scheduled day at about the same time, either with or without food
  • FARYDAK capsules should be swallowed whole with a cup of water. Do not open, crush, or chew the capsules
  • If a dose is missed it can be taken up to 12 hours after the specified dose time. If vomiting occurs the patient should not repeat the dose, but should take the next usual scheduled dose.
  • Counsel patients on the correct dosing schedule, technique of administration of FARYDAK, and when to take FARYDAK if dosing adjustments are made.

Monitoring

Prior to the start of FARYDAK treatment and during treatment, monitoring should include:

  • Complete Blood Count (CBC): Obtain a CBC before initiating treatment. Verify that the baseline platelet count is at least 100 x 109/L and the baseline absolute neutrophil count (ANC) is at least 1.5 x 109/L. Monitor the CBC weekly (or more often as clinically indicated) during treatment.
  • ECG: Perform an ECG prior to the start of therapy and repeat periodically during treatment as clinically indicated. Verify that the QTcF is less than 450 msec prior to initiation of treatment with FARYDAK. If during treatment with FARYDAK, the QTcF increases to ≥480 msec, interrupt treatment. Correct any electrolyte abnormalities. If QT prolongation does not resolve, permanently discontinue treatment with FARYDAK. During the clinical trial, ECGs were performed at baseline and prior to initiation of each cycle for the first 8 cycles.
  • Serum Electrolytes: Obtain electrolytes, including potassium and magnesium, at baseline and monitor during therapy. Correct abnormal electrolyte values before treatment. During the trial, monitoring was conducted prior to the start of each cycle, at Day 11 of cycles 1 to 8, and at the start of each cycle for cycles 9 to 16.

For additional information please refer to the bortezomib and dexamethasone prescribing information.

IV Compatibility

There is limited information regarding the compatibility of Panobinostat and IV administrations.

Overdosage

There is limited information regarding Panobinostat overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Panobinostat
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Mechanism of Action

There is limited information regarding Panobinostat Mechanism of Action in the drug label.

Structure

There is limited information regarding Panobinostat Structure in the drug label.

Pharmacodynamics

There is limited information regarding Panobinostat Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Panobinostat Pharmacokinetics in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Clinical Studies

There is limited information regarding Panobinostat Clinical Studies in the drug label.

How Supplied

Capsules: 10 mg, 15 mg, and 20 mg panobinostat (equivalent to 12.58 mg, 18.86 mg, and 25.15 mg respectively of panobinostat lactate)

10 mg: Size #3 light green opaque capsule, radial markings on cap with black ink “LBH 10 mg” and two radial bands with black ink on body, containing white to almost white powder.

15 mg: Size #1 orange opaque capsule, radial markings on cap with black ink “LBH 15 mg” and two radial bands with black ink on body, containing white to almost white powder.

20 mg: Size #1 red opaque capsule, radial markings on cap with black ink “LBH 20 mg” and two radial bands with black ink on body, containing white to almost white powder.

Storage

There is limited information regarding Panobinostat Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

This image is provided by the National Library of Medicine.

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Patient Counseling Information

There is limited information regarding Panobinostat Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Panobinostat interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Panobinostat Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Panobinostat Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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