Panobinostat (Farydak) — Clinical FAQs

Question 1

What is Panobinostat FDA-approved to treat?

Accepted Answer

Panobinostat is FDA-approved for the following oncology indications: 1. Relapsed and/or refractory multiple myeloma — in combination with bortezomib and dexamethasone, in patients who have received at least 2 prior standard-of-care regimens including bortezomib and an immunomodulatory agent (IMiD; FDA approved February 23, 2015; accelerated approval based on progression-free survival from the PANORAMA-1 trial).

Question 2

How does Panobinostat work (mechanism of action)?

Accepted Answer

Panobinostat is a hydroxamic acid pan-deacetylase (pan-HDAC) inhibitor with potent activity against all class I (HDAC1, 2, 3, 8), class II (HDAC4, 5, 6, 7, 9, 10), and class IV (HDAC11) zinc-dependent deacetylases. By chelating the catalytic zinc ion, panobinostat blocks histone deacetylation, resulting in global histone hyperacetylation (H3, H4), chromatin relaxation, and transcriptional reactivation of silenced tumor-suppressor genes. In multiple myeloma, the critical mechanistic rationale is disruption of aggresome-mediated protein degradation — an alternative misfolded-protein clearance pathway that myeloma cells depend upon when proteasomal activity is simultaneously inhibited by bortezomib. Dual blockade of both proteasomal and aggresomal protein degradation overwhelms myeloma plasma cells' capacity for proteostasis, leading to lethal proteotoxic stress and apoptosis. Panobinostat is approximately 10-fold more potent than vorinostat in vitro against class I HDAC isoforms and demonstrates synergistic cytotoxicity with proteasome inhibitors in preclinical myeloma models.

Question 3

How is Panobinostat administered?

Accepted Answer

Panobinostat is administered Oral (PO). Administer panobinostat 20 mg orally once every other day for 3 doses per week (e.

Question 4

What are the most common side effects of Panobinostat?

Accepted Answer

The most commonly reported side effects of Panobinostat (≥10% incidence) include: Thrombocytopenia (97%; Grade 3/4 ~67% — profound, expected, and primary dose-limiting toxicity), Diarrhea (68%; Grade 3/4 ~25%), Fatigue / asthenia (60%), Nausea (36%), Peripheral edema (29%) and others (14 total). Consult your oncologist for complete prescribing information.

Question 5

Does Panobinostat have a black box warning?

Accepted Answer

Yes. Panobinostat carries FDA black box warning(s) regarding: 1. Severe and fatal cardiac events: Ischemic heart disease, severe arrhythmias, and ST-segment changes have occurred in patients receiving panobinostat. Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG at baseline and periodically during treatment. Do not initiate panobinostat if QTcF >480 ms. Monitor and correct electrolyte abnormalities before and during treatment. Avoid concomitant use of drugs known to prolong the QT interval. Discontinue panobinostat if QTcF increases to >=500 ms. 2. Severe diarrhea: Severe diarrhea (Grade 3/4) occurred in approximately 25% of panobinostat-treated patients in clinical trials. Monitor patients for diarrhea and institute antidiarrheal agents (loperamide) at the first sign of loose or abnormal stools. Interrupt panobinostat for Grade 2 or greater diarrhea and permanently discontinue for Grade 3/4 diarrhea persisting despite antidiarrheal therapy.

Question 6

Is Panobinostat safe during pregnancy?

Accepted Answer

Panobinostat pregnancy safety: Can cause fetal harm. Animal reproductive studies demonstrate embryofetal toxicity including resorptions and malformations. Females of reproductive potential must use highly effective contraception during treatment and for at least 3 months after the last dose. Males with female partners of reproductive potential should use contraception during treatment and for at least 6 months after the last dose. Verify pregnancy status before initiation.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Panobinostat — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms