FDA approves panobinostat for treatment of multiple myeloma

Approval Date: February 23, 2015.

  • The U.S. Food and Drug Administration approved panobinostat for the treatment of patients with multiple myeloma.
  • FARYDAK (panobinostat lactate) is a histone deacetylase inhibitor.
  • The chemical name of panobinostat lactate is 2-Hydroxypropanoic acid, compd. with 2-(E)-N-hydroxy-3-[4­[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (1:1).
  • The structural formula is:


——————————–Mechanism of Action ————————————–

  • Panobinostat is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs at nanomolar concentrations.
  • HDACs catalyze the removal of acetyl groups from the lysine residues of histones and some non-histone proteins.
  • Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation.
  • In vitro, panobinostat caused the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells.
  • Increased levels of acetylated histones were observed in xenografts from mice that were treated with panobinostat.
  • Panobinostat shows more cytotoxicity towards tumor cells compared to normal cells

————————–INDICATIONS AND USAGE—————————-­

  • Panobinostat , 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.


  • 20 mg, taken orally once every other day for 3 doses per week (on Days 1, 3, 5, 8, 10, and 12) of Weeks 1 and 2 of each 21-day cycle for 8 cycles
  • Consider continuing treatment for an additional 8 cycles for patients with clinical benefit, unless they have unresolved severe or medically significant toxicity.

 ———————–DOSAGE FORMS AND STRENGTHS——————————-­

  • Capsules: 10 mg, 15 mg, and 20 mg.

 ———————–WARNINGS AND PRECAUTIONS——————————­

  • Severe diarrhea occurred in 25% of panobinostat treated patients. Monitor for symptoms, institute anti-diarrheal treatment, interrupt panobinostat and then reduce dose or discontinue panobinostat .
  • Severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes have occurred in patients receiving panobinostat . Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at baseline and periodically during treatment as clinically indicated.
  • Hemorrhage: Fatal and serious cases of gastrointestinal and pulmonary hemorrhage. Monitor platelet counts and transfuse as needed.
  • Hepatotoxicity: Monitor hepatic enzymes and adjust dosage if abnormal liver function tests are observed during panobinostat therapy.
  • Embryo-Fetal Toxicity: can cause fetal harm. Advise women of the potential hazard to the fetus and to avoid pregnancy while taking panobinostat .

 ——————————–ADVERSE REACTIONS—————————————­

  • The most common adverse reactions (incidence of at least 20%) in clinical studies are diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting.
  • The most common non-hematologic laboratory abnormalities (incidence ≥ 40%) are hypophosphatemia, hypokalemia, hyponatremia, and increased creatinine.
  • The most common hematologic laboratory abnormalities (incidence ≥60%) are thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia.

                ——————————DRUG INTERACTIONS———————————–—-­

  • Strong CYP3A4 inhibitors: Reduce drug dose.
  • Strong CYP3A4 inducers: Avoid concomitant use with panobinostat .
  • Sensitive CYP2D6 substrates: Avoid concomitant use with panobinostat .
  • Anti-arrhythmic drugs/QT-prolonging drugs: Avoid concomitant use.

                     ————————-USE IN SPECIFIC POPULATIONS——————-–­

  • Hepatic Impairment: Hepatic impairment can increase panobinostat exposure.
  • Reduce panobinostat dose in patients with mild or moderate hepatic impairment.
  • Avoid use in patients with severe hepatic impairment.

Farydak is marketed by East Hanover, New Jersey-based Novartis Pharmaceuticals.

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