II. Indications
- Multiple Myeloma (relapsed)
III. Mechanism
- Antimetabolite, Antineoplastic Agent
-
Histone Deacetylase Inhibitor (HDAC Inhibitor, cinnamic hydroxamic acid analog)
- Histones are the spools around which DNA are wrapped, and which play a role in gene expression
- Cancers may be facilitated by abnormally expressed genes in specific histone regions
- HDAC Inhibitors block histone deacetylase
- Histone deacetylase is an enzyme that catalyzes removal of acetyl groups from core histones
- Results in hyperacetylation of histones, suppressing gene expression and cell differentiation
- Panobinostat, by selectively inhibiting HDAC, triggers Cell Cycle arrest in the G2/M phase
- Histones are the spools around which DNA are wrapped, and which play a role in gene expression
- Panobinostat also modulates Angiogenesis-related genes, blocking endothelial cell chemotaxis and invasion
- Hypoxia-inducible factor-1alpha (HIF-1a)
- Vascular Endothelial Growth Factor (VEGF)
IV. Medications
- Capsules: 10, 15 and 20 mg
V. Dosing
- See other references for disease specific dosing protocols
-
Multiple Myeloma
- Panobinostat 20 mg every other day for first 2 weeks of 21 day cycles for 8 cycles
- Combined with Bortezomib and Dexamethasone
- Richardson (2016) Blood 127(6):713-21 +PMID: 26631116 [PubMed]
VI. Adverse Effects
- Diarrhea (severe in 25% of patients)
- Cardiovascular Effects (Life-threatening, deaths have occurred)
- Acute Coronary Syndrome
- Cardiac Arrhythmia (esp. if concurrent Electrolyte abnormalities)
-
Hemorrhage (severe)
- Life threatening pulmonary and gastrointestinal Hemorrhage have occurred
- Increased risk with significant Thrombocytopenia
- Hepatotoxicity
VII. Safety
- Avoid in Pregnancy (any trimester)
- Use reliable Contraception
- Avoid in Lactation
- Monitoring (including baseline)
VIII. Drug Interactions
- Strong CYP3A4 Inhibitors (e.g. Clarithromycin, Erythromycin, Itraconazole, Ketoconazole, Ritonavir, Diltiazem, Verapamil)
- Reduce Panobinostat dose
- Strong CYP3A4 Inducers (e.g. Rifampin, Phenytoin and Ritonavir)
- Avoid in combination with Panobinostat
-
CYP2D6 Substrates (e.g. Desipramine, Dextromethorphan, Nebivolol)
- Avoid in combination with Panobinostat
-
Antiarrhythmic Agents
- Avoid in combination with Panobinostat
-
Medication Causes of QTc Prolongation
- Avoid in combination with Panobinostat