Panobinostat

FARYDAK

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Pronunciation: pan-oe-BIN-oe-stat (FAIR-i-dak)

Panobinostat ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Panobinostat ballicule

What it isHistone deacetylase inhibitor; multiple myeloma.

Why this oneIt adds an epigenetic mechanism to proteasome inhibition in refractory disease.

What limits itSevere diarrhea and cardiac arrhythmia, including QT prolongation. Thrombocytopenia; withdrawn in some markets.

Panobinostat molecular structure (skeletal formula) — Molecular structure: Panobinostat

FDA-approved for

multiple myeloma (2015)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Fatal and serious toxicities: severe diarrhea (25%) and severe/fatal cardiac ischemic events, arrhythmias, and ECG changes; monitor and manage.

FDA dosing	Population	Start	Target	Max
Multiple myeloma (relapsed; w/ bortezomib + dexamethasone)	Adults	20 mg 3×/week (D1,3,5,8,10,12) wks 1–2 of 21-day cycle	20 mg	20 mg

Renal Mild–severe: no adjustment (no effect on exposure); not studied in ESRD/dialysis.

Hepatic Mild: reduce start to 15 mg. Moderate: reduce start to 10 mg. Severe: avoid.

Reduce dose in 5 mg steps (20→15→10); discontinue if <10 mg 3×/week. Up to 16 cycles total. Given with bortezomib + dexamethasone.

Instructions

Swallow capsules whole with water; do not open, crush, or chew
Take with or without food at about the same time on each scheduled day
If a dose is missed, take up to 12 h after scheduled time
If vomiting occurs, do not repeat the dose; take next scheduled dose
With strong CYP3A inhibitors, reduce start to 10 mg

Available strengths

cap 10, 15, 20 mg

Cautions

Severe diarrhea
Cardiac toxicities: ischemia, arrhythmias, QT prolongation
Fatal/serious GI and pulmonary hemorrhage
Myelosuppression: thrombocytopenia, neutropenia, anemia
Infections (including fatal)
Hepatotoxicity
Embryo-fetal toxicity

Adverse reactions

Diarrhea, nausea, vomiting, decreased appetite
Fatigue, peripheral edema, pyrexia
Labs: thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemia; hypophosphatemia, hypokalemia, hyponatremia, increased creatinine

Pregnancy Can cause fetal harm; teratogenic in rats and rabbits.

Lactation Unknown whether excreted in milk; decide to discontinue nursing or drug.

Cost

Panobinostat (FARYDAK)

Strength		#/mo	CostPlus
10 mg	cap	per unit	not offered
15 mg	cap	per unit	not offered
20 mg	cap	per unit	not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Panobinostat is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

⚠ BOXED WARNINGS

Severe diarrhea
Cardiac toxicity

Classes and tags

Clinical profile

Therapeutic safety burden4 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability1 / 4

QT / Torsades4 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Defining liabilitySevere diarrhea, cytopenias, bleeding and cardiac toxicity

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