Warnings and Precautions, Embryo-Fetal Toxicity (5.7)

6/2016

FARYDAK, 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. (1)
DOSAGE AND ADMINISTRATION

• 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 (2.1)
• Consider continuing treatment for an additional 8 cycles for patients with clinical benefit, unless they have unresolved severe or medically significant toxicity (2.1)

DOSAGE FORMS AND STRENGTHS
Capsules: 10 mg, 15 mg, and 20 mg panobinostat (equivalent to 12.58 mg, 18.86 mg, and 25.15 mg respectively of panobinostat lactate) (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS

• Hemorrhage: Fatal and serious cases of gastrointestinal and pulmonary hemorrhage. Monitor platelet counts and transfuse as needed. (5.3)
• Hepatotoxicity: Monitor hepatic enzymes and adjust dosage if abnormal liver function tests are observed during FARYDAK therapy. (5.6)
• Embryo-Fetal Toxicity: can cause fetal harm. Advise women of the potential hazard to the fetus and to avoid pregnancy while taking FARYDAK. (5.7)

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. (6.1)

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. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Strong CYP3A4 inhibitors: Reduce FARYDAK dose. (7.1)
• Strong CYP3A4 inducers: Avoid concomitant use with FARYDAK. (7.2)
• Sensitive CYP2D6 substrates: Avoid concomitant use with FARYDAK. (7.3)
• Anti-arrhythmic drugs/QT-prolonging drugs: Avoid concomitant use. (7.4)

USE IN SPECIFIC POPULATIONS

Hepatic Impairment: Hepatic impairment can increase panobinostat exposure. Reduce FARYDAK dose in patients with mild or moderate hepatic impairment. Avoid use in patients with severe hepatic impairment. (8.6)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.