Panobinostat

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Information about Panobinostat

Panobinostat is an oral histone deacetylase inhibitor and antineoplastic agent that is approved for use in combination with other agents in refractory or relapsed multiple myeloma. 

Liver safety of Panobinostat

Panobinostat is associated with modest rate of minor serum enzyme elevations during therapy, but has not been linked to cases of clinically apparent liver injury

Mechanism of action of Panobinostat

Panobinostat (pan" oh bin' oh stat) is an oral small molecule inhibitor of histone deacetylases, thereby preventing removal of acetyl groups from histones.  The accumulation of acetyl groups on histones causes cell cycle arrest and apoptotic cell death.  Malignant cells are particularly sensitive to the effects of inhibition of histone deacetylases.  In open label studies in patients with multiple myeloma, panobinostat in combination with bortezomib (a proteasome inhibitor) yielded overall response rates of up to 50% and some responders had long term remissions.  A large, controlled trial in patients with advanced, refractory multiple myeloma demonstrated prolongation of progression-free survival by the addition of panobinostat to bortezomib and dexamethasone, but the overall survival was not different at the time of the initial analysis.  Nevertheless, panobinostat was given accelerated approval for use in the United States in 2015 to be used in combination with bortezomib and dexamethasone in patients with refractory or relapsed multiple myeloma

Dosage and administration for Panobinostat

Panobinostat is available in capsules of 10, 15 or 20 mg under the brand name Farydak.  The recommended dose regimen is 20 mg three times weekly for two weeks in three week cycles until there is disease progression or unacceptable toxicity.  side effects are common and may require dose modification. 

Side effects of Panobinostat

The most common adverse events are thrombocytopenia, leukopenia, anemia, diarrhea, nausea, vomiting, anorexia, fatigue, fever, peripheral edema, cough and pruritus.  Panobinostat therapy has also been associated with hypokalemia, hypophosphatemia, hyponatremia and mild increases in serum creatinine.  Uncommon, but serious adverse events include severe diarrhea and cardiovascular events such as cardiac ischemia, arrhythmias and EKG changes. 

 


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