Panobinostat Brand Name– FARYDAK
What is Panobinostat
Panobinostat is a histone deacetylase (HDAC) inhibitor that works by blocking the enzymatic activity of HDAC causing increased acetylation of histone proteins leading to transcriptional activation.
The accumulation of acetylated histones and other proteins resulted in cell cycle arrest and/or apoptosis of some transformed cells in vitro.
Panobinostat is indicated in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent.
At a median follow-up time of 6.47 months (interquartile range, 1.81 to 13.47 months), the median progression-free survival (PFS) time was significantly improved in patients with relapsed or relapsed and refractory multiple myeloma who received panobinostat, bortezomib, and dexamethasone (11.99 months) compared with placebo, bortezomib, and dexamethasone (8.08 months; hazard ratio (HR) = 0.63; 95% CI, 0.52 to 0.76; p < 0.0001) in a multinational, double-blind, randomized, phase III trial (the PANORAMA1 trial; n = 768).
The overall survival (OS) time was not significantly improved in the panobinostat arm compared with placebo arm (33.64 months vs. 30.39 months; HR = 0.87; 95% CI, 0.69 to 1.1); however, OS data are not mature.
Panobinostat (Farydak) was approved by the FDA in February 2015. It was an accelerated approval based on PFS data; however, continued approval may be dependent upon verification and description of clinical benefit in confirmatory trials.
Indications
- cutaneous T-cell lymphoma (CTCL)
- multiple myeloma
For the treatment of multiple myeloma in patients who have received at least 2 prior therapies (including bortezomib and an immunomodulatory agent), in combination with bortezomib and dexamethasone
NOTE: Panobinostat has been designated as an orphan drug by the FDA.
Side Effects
- abdominal pain
- anemia
- anemia
- anorexia
- anorexia
- asthenia
- asthenia
- atrial fibrillation
- atrial flutter
- atrial tachycardia
- bleeding
- bradycardia
- cardiac arrest
- cardiotoxicity
- cheilitis
- chills
- colitis
- cough
- dehydration
- diarrhea
- diarrhea
- dizziness
- dysgeusia
- dyspepsia
- dyspnea
- elevated hepatic enzymes
- erythema
- fatigue
- fatigue
- fever
- fever
- flatulence
- fluid retention
- gastritis
- GI bleeding
- headache
- hepatitis
- hyperbilirubinemia
- hyperbilirubinemia
- hyperglycemia
- hypermagnesemia
- hypermagnesemia
- hyperphosphatemia
- hyperphosphatemia
- hypertension
- hyperuricemia
- hypoalbuminemia
- hypoalbuminemia
- hypocalcemia
- hypocalcemia
- hypokalemia
- hypokalemia
- hypomagnesemia
- hyponatremia
- hyponatremia
- hypophosphatemia
- hypophosphatemia
- hypotension
- hypothyroidism
- infection
- insomnia
- lethargy
- lethargy
- leukopenia
- leukopenia
- lymphopenia
- lymphopenia
- malaise
- malaise
- nausea
- nausea
- neutropenia
- neutropenia
- orthostatic hypotension
- palpitations
- peripheral edema
- peripheral edema
- QT prolongation
- rash
- renal failure (unspecified)
- respiratory arrest
- sinus tachycardia
- skin ulcer
- supraventricular tachycardia (SVT)
- supraventricular tachycardia (SVT)
- syncope
- thrombocytopenia
- thrombocytopenia
- tremor
- urinary incontinence
- ventricular tachycardia
- vomiting
- vomiting
- weight loss
- weight loss
- wheezing
- xerostomia
Monitoring Parameters
- CBC with differential
- ECG
- LFTs
- pregnancy testing
- serum electrolytes
Contraindications
- anemia
- angina
- apheresis
- AV block
- bleeding
- bradycardia
- breast-feeding
- cardiac arrhythmias
- cardiomyopathy
- cardiotoxicity
- celiac disease
- children
- contraception requirements
- dehydration
- diarrhea
- electrolyte imbalance
- females
- fever
- fungal infection
- geriatric
- GI bleeding
- heart failure
- hepatic disease
- human immunodeficiency virus (HIV) infection
- hyperparathyroidism
- hypocalcemia
- hypokalemia
- hypomagnesemia
- hypothermia
- hypothyroidism
- infants
- infection
- infertility
- long QT syndrome
- male-mediated teratogenicity
- myocardial infarction
- nausea/vomiting
- neonates
- neutropenia
- pheochromocytoma
- pregnancy
- pregnancy testing
- pulmonary bleeding
- QT prolongation
- reproductive risk
- rheumatoid arthritis
- sickle cell disease
- sleep deprivation
- stroke
- systemic lupus erythematosus (SLE)
- thrombocytopenia
- viral infection
Interactions
- Acetaminophen; Butalbital; Caffeine; Codeine
- Acetaminophen; Caffeine; Dihydrocodeine
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Codeine
- Acetaminophen; Dextromethorphan
- Acetaminophen; Dextromethorphan; Doxylamine
- Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
- Acetaminophen; Dextromethorphan; Phenylephrine
- Acetaminophen; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Hydrocodone
- Acetaminophen; Tramadol
- Aclidinium; Formoterol
- Albuterol
- Albuterol; Ipratropium
- Alfuzosin
- Amiodarone
- Amitriptyline
- Amitriptyline; Chlordiazepoxide
- Amoxicillin; Clarithromycin; Lansoprazole
- Amoxicillin; Clarithromycin; Omeprazole
- Anagrelide
- Apalutamide
- Apomorphine
- Aprepitant, Fosaprepitant
- Arformoterol
- Aripiprazole
- Arsenic Trioxide
- Artemether; Lumefantrine
- Asenapine
- Aspirin, ASA; Butalbital; Caffeine; Codeine
- Aspirin, ASA; Caffeine; Dihydrocodeine
- Aspirin, ASA; Carisoprodol; Codeine
- Atazanavir; Cobicistat
- Atomoxetine
- Atropine; Hyoscyamine; Phenobarbital; Scopolamine
- Azithromycin
- Bedaquiline
- Belladonna Alkaloids; Ergotamine; Phenobarbital
- Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
- Bismuth Subsalicylate; Metronidazole; Tetracycline
- Boceprevir
- Brexpiprazole
- Brompheniramine; Dextromethorphan; Guaifenesin
- Brompheniramine; Dextromethorphan; Phenylephrine
- Brompheniramine; Guaifenesin; Hydrocodone
- Brompheniramine; Hydrocodone; Pseudoephedrine
- Budesonide; Formoterol
- Buprenorphine
- Buprenorphine; Naloxone
- Carbamazepine
- Carbinoxamine; Dextromethorphan; Pseudoephedrine
- Carbinoxamine; Hydrocodone; Phenylephrine
- Carbinoxamine; Hydrocodone; Pseudoephedrine
- Ceritinib
- Chloroquine
- Chlorpheniramine; Codeine
- Chlorpheniramine; Dextromethorphan
- Chlorpheniramine; Dextromethorphan; Phenylephrine
- Chlorpheniramine; Dihydrocodeine; Phenylephrine
- Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
- Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
- Chlorpheniramine; Hydrocodone
- Chlorpheniramine; Hydrocodone; Phenylephrine
- Chlorpheniramine; Hydrocodone; Pseudoephedrine
- Chlorpromazine
- Ciprofloxacin
- Cisapride
- Citalopram
- Clarithromycin
- Clofazimine
- Clomipramine
- Clozapine
- Cobicistat
- Codeine
- Codeine; Guaifenesin
- Codeine; Phenylephrine; Promethazine
- Codeine; Promethazine
- Conivaptan
- Crizotinib
- Daclatasvir
- Darunavir; Cobicistat
- Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
- Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
- Dasatinib
- Degarelix
- Desflurane
- Desipramine
- Deutetrabenazine
- Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
- Dextromethorphan
- Dextromethorphan; Diphenhydramine; Phenylephrine
- Dextromethorphan; Guaifenesin
- Dextromethorphan; Guaifenesin; Phenylephrine
- Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate
- Dextromethorphan; Guaifenesin; Pseudoephedrine
- Dextromethorphan; Promethazine
- Dextromethorphan; Quinidine
- Dihydrocodeine; Guaifenesin; Pseudoephedrine
- Diphenhydramine; Hydrocodone; Phenylephrine
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- Dolasetron
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- Elbasvir; Grazoprevir
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- Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
- Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
- Emtricitabine; Rilpivirine; Tenofovir alafenamide
- Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
- Encorafenib
- Enflurane
- Entrectinib
- Enzalutamide
- Eribulin
- Erythromycin
- Erythromycin; Sulfisoxazole
- Escitalopram
- Ezogabine
- Fingolimod
- Flecainide
- Fluconazole
- Fluoxetine
- Fluoxetine; Olanzapine
- Fluticasone; Salmeterol
- Fluticasone; Umeclidinium; Vilanterol
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- Fluvoxamine
- Formoterol
- Formoterol; Mometasone
- Fosamprenavir
- Foscarnet
- Fosphenytoin
- Fostemsavir
- Gefitinib
- Gemifloxacin
- Gemtuzumab Ozogamicin
- Gilteritinib
- Glasdegib
- Glecaprevir; Pibrentasvir
- Glycopyrrolate; Formoterol
- Goserelin
- Granisetron
- grapefruit juice
- Guaifenesin; Hydrocodone
- Guaifenesin; Hydrocodone; Pseudoephedrine
- Halogenated Anesthetics
- Haloperidol
- Halothane
- Histrelin
- Homatropine; Hydrocodone
- Hydrochlorothiazide, HCTZ; Metoprolol
- Hydrocodone
- Hydrocodone; Ibuprofen
- Hydrocodone; Phenylephrine
- Hydrocodone; Potassium Guaiacolsulfonate
- Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
- Hydrocodone; Pseudoephedrine
- Hydroxychloroquine
- Hydroxyzine
- Ibutilide
- Iloperidone
- Imipramine
- Indacaterol
- Indacaterol; Glycopyrrolate
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- Inotuzumab Ozogamicin
- Isoflurane
- Itraconazole
- Ivosidenib
- Ketoconazole
- Lapatinib
- Lefamulin
- Lenvatinib
- Letermovir
- Leuprolide
- Leuprolide; Norethindrone
- Levalbuterol
- Levofloxacin
- Lithium
- Lofexidine
- Long-acting beta-agonists
- Loperamide
- Loperamide; Simethicone
- Lopinavir; Ritonavir
- Lumacaftor; Ivacaftor
- Macimorelin
- Maprotiline
- Mefloquine
- Meperidine; Promethazine
- Metaproterenol
- Methadone
- Metoprolol
- Metronidazole
- Mexiletine
- Midostaurin
- Mifepristone
- Mirtazapine
- Mitotane
- Nebivolol
- Nebivolol; Valsartan
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- Nelfinavir
- Nilotinib
- Norfloxacin
- Nortriptyline
- Octreotide
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- Oxaliplatin
- Ozanimod
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- Perphenazine
- Perphenazine; Amitriptyline
- Phenobarbital
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- Phenytoin
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- Pitolisant
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- Quetiapine
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- Quinine
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- Ribociclib
- Ribociclib; Letrozole
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- Romidepsin
- Salmeterol
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- Sevoflurane
- Short-acting beta-agonists
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- Vandetanib
- Vardenafil
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- Vorinostat
- Ziprasidone
- Zonisamide
