Panobinostat Disease Interactions

Severe and fatal cardiac ischemic events, as well as severe arrhythmias, and electrocardiogram (ECG) changes have occurred in patients receiving panobinostat. Panobinostat may prolong cardiac ventricular repolarization (QT interval). Do not initiate treatment with panobinostat in patients with a QTcF >450 msec or clinically significant baseline ST-segment or T-wave abnormalities. If during treatment, the QTcF increases to >=480 msec, interrupt treatment. Arrhythmias may be exacerbated by electrolyte abnormalities. It is recommended to obtain ECG at baseline and periodically during treatment as clinically indicated. Monitor patient hydration status and electrolyte blood levels, including potassium, magnesium and phosphate, at baseline and frequently as clinically indicated during therapy and correct to prevent dehydration and electrolyte disturbances. If QT prolongation does not resolve, permanently discontinue treatment with panobinostat.

Hepatic impairment can increase panobinostat exposure. It is recommended to reduce the starting dose of panobinostat in patients with mild or moderate hepatic impairment. Avoid the use of panobinostat in patients with severe hepatic impairment. Liver function should be monitored prior to treatment and regularly during treatment. If abnormal liver function tests are observed dose adjustments might be considered and the patient should be followed until values return to normal or to pretreatment levels.

Localized and systemic infections, including pneumonia, bacterial infections, invasive fungal infections, and viral infections have been reported in patients taking panobinostat. It is recommended to monitor patients for signs and symptoms of infections during treatment; if a diagnosis of infection is made, institute appropriate anti-infective treatment promptly and consider interruption or discontinuation of therapy. Care should be exercised when prescribing this agent to patients at risk.

Panobinostat causes myelosuppression. Cases of severe thrombocytopenia, neutropenia and anemia have been reported with the use of panobinostat. It is recommended to obtain a baseline CBC and monitor the CBC frequently as clinically indicated. Dose modifications are recommended for myelosuppression.

Mild renal impairment to severe renal impairment did not impact the plasma exposure of panobinostat. The use of panobinostat has not been studied in patients with end stage renal disease or patients on dialysis. Care should be exercised when using panobinostat in these patients as the dialyzability of panobinostat is unknown.