• Treatment of multiple myeloma (with bortezomib and dexamethasone) that has not responded to two previous treatments including bortezomib and an immunomodulator.

Contraindicated in:

• Severe hepatic impairment
• Recent MI or unstable angina
• Concurrent use of CYP3A4 inducers (may ↓ effectiveness)
• Concurrent use of antiarrhythmics or QT-interval prolonging drugs (↑ risk of serious cardiovascular reactions)
• Concurrent use of CYP2D6 substrates (alteration of blood levels may result in serious adverse effects)
• OB: May cause fetal harm
• Lactation: Discontinue breastfeeding or discontinue panobinostat.

Use Cautiously in:

• Electrolyte abnormalities (↑ risk of cardiac toxicity, correct prior to treatment)
• Mild/moderate hepatic impairment (↓ dose recommended)
• End stage renal disease/dialysis
• Geri: ↑risk of adverse cardiac, GI and hematologic reactions (more frequent monitoring recommended)
• Women of reproductive potential and sexually active men
• Pedi: Safety and effectiveness not established.

CNS: fatigue, weakness, dizziness, headache, syncope.

Resp: cough, dyspnea, respiratory failure, rales, wheezing.

CV: ARRHYTHMIAS, ISCHEMIA, QT INTERVAL PROLONGATION, hypertension, hypotension, orthostatic hypotension, palpitations, peripheral edema.

GI: diarrhea, ↓appetite, nausea, vomiting, abdominal distention, abdominal pain, cheilitis, colitis, dry mouth, dysgeusia, dyspepsia, flatulence, gastrointestinal pain, hepatic dysfunction.

GU: renal impairment, urinary incontinence.

Derm: erythema, rash, skin lesions.

Endo: hyperglycemia, hypothyroidism.

F and E: hypermagnesemia, hyperphosphatemia, hypocalcemia, hypokalemia, hypophosphatemia, dehydration, hypomagnesemia, hyponatremia.

Hemat: BLEEDING, anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia.

Metab: hyperuricemia.

MS: joint swelling.

Neuro: tremor.
Misc: FEBRILE NEUTROPENIA, fever.

Drug-Drug:

• ↑blood levels and risk of toxicity with strong inhibitors of CYP3A including clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, , nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole; ↓ panobinostat dose to 10 mg/day.
• ↓blood levels and effectiveness with strong CYP3A inducers; avoid concurrent use.
• May ↑ levels and risk of toxicity of CYP2D6 substrates including atomoxetine, desipramine, dextromethorphan, metoprolol, nevibolol, perphenazine, pimozide, thioridazine, tolterodine, and venlafaxine; avoid concurrent use, but if necessary close clinical monitoring is required.
• ↑risk of adverse cardiovascular reactions with some antiarrhythmics and drugs known to prolong the QT interval including clarithromycin, chloroquine, methadone, moxifloxacin and pimozide; concurrent use is not recommended.
• Antiemetics known to prolong the QT interval including dolasetron and ondansetron may be used with frequent ECG monitoring.

Drug-Food:

• ↑blood levels and risk of toxicity with foods that are CYP3A inhibitors including grapefruit/grapefruit juice, pomegranate/pomegranate juice and star fruit; avoid these foods.

• Capsules: 10 mg; 15 mg; 20 mg;

• PO (Adults): 20 mg every other day for 3 doses every wk (days 1, 3, 5, 8, 10 and 12) for 2 wk of every 21–day cycle for 8 cycles; an additional 8 cycles may be added if there is clinical benefit without dangerous toxicity. Given concurrently with bortezomib and dexamethasone. Dose reduction/interruption/alteration/discontinuation may be required for gastrointestinal or hematologic toxicity. Concurrent use of strong CYP3A4 inhibitors — ↓starting dose to 10 mg.

Farydak

• Acts as an inhibitor of the enzyme histone deacetylase (HDAC), resulting in cell cycle arrest/apoptosis; cytotoxicity is enhanced in tumor cells.

• Decreased progression of multiple myeloma.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

Absorption: 21% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized; 40% by CYP3A4, remainder by other systems including CYP2D6. 29–51% excreted in urine, 44–77% excreted in feces, mostly as metabolites. <2.5% excreted in urine unchanged, <5% excreted in feces unchanged.

Half-life: 37 hr.

(improvement in progression-free interval)

• Instruct patient to take panobinostat as directed. Take missed dose as soon as possible within 12 hrs or wait until next scheduled dose. If vomiting occurs, do not repeat dose, take next dose at scheduled time. Advise patient to read Medication Guide prior to starting and with each Rx refill in case of changes.
• Caution patient to avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice during therapy.
• Advise patient to notify health care professional immediately if signs and symptoms of heart problems (chest pain or discomfort, changes in heart beat (fast or slow), palpitations, lightheadedness, fainting, dizziness, blue discoloration of lips, shortness of breath, swelling of lower limbs or skin), bleeding (blood in stools or black stools, pink or brown urine, unexpected bleeding or severe uncontrollable bleeding, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, feeling dizzy or weak, confusion, change in speech, headache that lasts a long time), infection, GI toxicities (nausea, vomiting, diarrhea, dehydration) or liver problems (feel tired or weak, loss of appetite, dark amber colored urine, upper abdominal (stomach) pain, yellowing of skin or white of eyes) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications during therapy.
• Caution female patient that panobinostat is teratogenic. Use effective contraception during and for at least 3 mo after therapy and avoid breastfeeding. Advise male patient to use condoms during and for at least 6 mo after last dose of panobinostat. Advise patient to notify health care professional if pregnancy occurs during therapy.
• Emphasize the need for lab tests periodically during therapy to monitor for adverse reactions.

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