Pharmacological Class:
Histone deacetylase (HDAC) inhibitor.
Active Ingredient(s):
Panobinostat 10mg, 15mg, 20mg; capsules.
Company
Novartis Pharmaceuticals Corp
Indication(s):
Multiple myeloma, in patients who have received at least two prior regimens (including bortezomib and an immunomodulatory agent), in combination with bortezomib and dexamethasone.
Pharmacology:
Panobinostat inhibits the enzymatic activity of HDACs at nanomolar concentrations which results in increased acetylation of histone proteins, leading to transcriptional activation. Accumulation of acetylated histones and other proteins induces cell cycle arrest and/or apoptosis of some transformed cells.
Clinical Trials:
The efficacy and safety of Farydak with bortezomib and dexamethasone was eva luated in a randomized, double-blind, placebo-controlled, multicenter study in 768 patients with relapsed multiple myeloma who had received 1–3 prior lines of therapy. Patients were randomized to bortezomib and dexamethasone with Farydak or placebo. The primary endpoint was progression-free survival (PFS). A prespecified subgroup analysis (n=193) showed the benefit:risk was greater in this heavily pretreated population than the overall trial population. The median PFS was 10.6 months in the Farydak arm vs. 5.8 months in the placebo arm (HR 0.52; [95% CI: 0.36, 0.76]).
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
Swallow whole with water. Take at same time on scheduled days. Initially 20mg once every other day for 3 doses/wk in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles. Consider 8 more cycles for patients with clinical benefit if no severe or significant toxicity; max 16 cycles (48 wks). Give with bortezomib inj and oral dexamethasone per scheduled day. Hepatic impairment: mild: initially 15mg; moderate: initially 10mg; severe: avoid. Concomitant strong CYP3A inhibitors: initially 10mg. Dose adjustments and modifications for toxicity: see full labeling.
Children:
Not established.
Warnings/Precautions:
Risk of severe diarrhea and cardiac toxicities. Monitor hydration and electrolytes at baseline, weekly during therapy, or more as indicated. Initiate antidiarrheals at onset of diarrhea; interrupt dose if 4–6 stools/day. Do not initiate if history of recent MI or unstable angina, QTcF >450msec, significant baseline ST-segment or T-wave abnormalities, active infections. Perform ECG prior to initiation and repeat during treatment as indicated. Correct electrolyte abnormalities prior to initiation and monitor; interrupt if QTcF ≥480msec; discontinue if QT prolongation does not resolve. Serious hemorrhage. Obtain CBC prior to initiation; monitor weekly during therapy or more as indicated. Monitor for infections; treat and consider interruption or discontinuation if diagnosed. Monitor liver function prior to and during treatment; consider dose adjustments if abnormal tests observed. ESRD or dialysis: not studied. Elderly: monitor for toxicity more frequently (esp. GI, myelosuppression, cardiac). Pregnancy: avoid. Obtain pregnancy test prior to and during treatment. Use effective contraception during and for ≥1 month after last dose; males: use condoms during and for ≥3 months after last dose. Nursing mothers: not recommended.
Interaction(s)
Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazol |
