HIGHLIGHTS OF PRESCRIBING INFORMATION -----------------------------CONTRAINDICATIONS-------------------------------- These highlights do not include all the information needed to use None (4) FARYDAK safely and effectively. See full prescribing information for FARYDAK. -----------------------WARNINGS AND PRECAUTIONS------------------------ Hemorrhage: Fatal and serious cases of gastrointestinal and pulmonary FARYDAK® (panobinostat) capsules, for oral use hemorrhage. Monitor platelet counts and transfuse as needed. (5.3) Initial U.S. Approval: 2015 Hepatotoxicity: Monitor hepatic enzymes and adjust dosage if abnormal liver function tests are observed during FARYDAK therapy. (5.6) WARNING: FATAL AND SERIOUS TOXICITIES: SEVERE Embryo-Fetal Toxicity: can cause fetal harm. Advise women of the DIARRHEA AND CARDIAC TOXICITIES potential hazard to the fetus and to avoid pregnancy while taking See full prescribing information for complete boxed warning. FARYDAK. (5.7) Severe diarrhea occurred in 25% of FARYDAK treated patients. Monitor for symptoms, institute anti-diarrheal treatment, --------------------------------ADVERSE REACTIONS----------------------------- interrupt FARYDAK and then reduce dose or discontinue The most common adverse reactions (incidence of at least 20%) in clinical FARYDAK. (5.1) studies are diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting. (6.1) Severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes have occurred in patients receiving FARYDAK. The most common non-hematologic laboratory abnormalities (incidence ≥ Arrhythmias may be exacerbated by electrolyte abnormalities. 40%) are hypophosphatemia, hypokalemia, hyponatremia, and increased Obtain ECG and electrolytes at baseline and periodically during creatinine. The most common hematologic laboratory abnormalities treatment as clinically indicated. (5.2) (incidence ≥60%) are thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia. (6.1) --------------------------INDICATIONS AND USAGE----------------------------- FARYDAK, a histone deacetylase inhibitor, in combination with bortezomib To report SUSPECTED ADVERSE REACTIONS, contact Novartis and dexamethasone, is indicated for the treatment of patients with multiple Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA- myeloma who have received at least 2 prior regimens, including bortezomib 1088 or www.fda.gov/medwatch. and an immunomodulatory agent. This indication is approved under accelerated approval based on progression free survival. Continued approval ------------------------------DRUG INTERACTIONS------------------------------- for this indication may be contingent upon verification and description of Strong CYP3A4 inhibitors: Reduce FARYDAK dose. (7.1) clinical benefit in confirmatory trials. (1) Strong CYP3A4 inducers: Avoid concomitant use with FARYDAK. (7.2) Sensitive CYP2D6 substrates: Avoid concomitant use with FARYDAK. ------------------------DOSAGE AND ADMINISTRATION---------------------- (7.3) 20 mg, taken orally once every other day for 3 doses per week (on Days 1, Anti-arrhythmic drugs/QT-prolonging drugs: Avoid concomitant use. (7.4) 3, 5, 8, 10, and 12) of Weeks 1 and 2 of each 21-day cycle for 8 cycles (2.1) -------------------------USE IN SPECIFIC POPULATIONS---------------------- Consider continuing treatment for an additional 8 cycles for patients with Hepatic Impairment: Hepatic impairment can increase panobinostat exposure. clinical benefit, unless they have unresolved severe or medically Reduce FARYDAK dose in patients with mild or moderate hepatic significant toxicity (2.1) impairment. Avoid use in patients with severe hepatic impairment. (8.6) -----------------------DOSAGE FORMS AND STRENGTHS-------------------- See 17 for PATIENT COUNSELING INFORMATION and Medication Capsules: 10 mg, 15 mg, and 20 mg (3) Guide Revised: 2/2015 FULL PRESCRIBING INFORMATION: CONTENTS* 7.3 Agents whose Plasma Concentrations May be Increased by WARNING: FATAL AND SERIOUS TOXICITIES: SEVERE FARYDAK DIARRHEA AND CARDIAC TOXICITIES 7.4 Drugs that Prolong QT interval 1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS 2 DOSAGE AND ADMINISTRATION 8.1 Pregnancy 2.1 Recommended Dosing 8.2 Lactation 2.2 Administration and Monitoring Instructions 8.3 Females and Males of Reproductive Potential 2.3 Dose Adjustments and Modifications for Toxicity 8.4 Pediatric Use 2.4 Dose Modifications for Use in Hepatic Impairment 8.5 Geriatric Use 2.5 Dose Modifications for Use with Strong CYP3A Inhibitors 8.6 Hepatic Impairment 3 DOSAGE FORMS AND STRENGTHS 8.7 Renal Impairment 4 CONTRAINDICATIONS 10 OVERDOSAGE 5 WARNINGS AND PRECAUTIONS 11 DESCRIPTION 5.1 Diarrhea 12 CLINICAL PHARMACOLOGY 5.2 Cardiac Toxicities 12.1 Mechanism of Action 5.3 Hemorrhage 12.2 Pharmacodynamics 5.4 Myelosuppression 12.3 Pharmacokinetics 5.5 Infections 13 NONCLINICAL TOXICOLOGY 5.6 Hepatotoxicity 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.7 Embryo-Fetal Toxicity 13.2 Animal Toxicology and/or Pharmacology 6 ADVERSE REACTIONS 14 CLINICAL STUDIES 6.1 Clinical Trials Experience 14.1 Relapsed Multiple Myeloma 7 DRUG INTERACTIONS 15 REFERENCES 7.1 Agents that May Increase FARYDAK Blood 16 HOW SUPPLIED/STORAGE AND HANDLING Concentrations 17 PATIENT COUNSELING INFORMATION 7.2 Agents that May Decrease FARYDAK Plasma Concentrations * Sections or subsections omitted from the full prescribing information are not listed Reference ID: 3699607 FULL PRESCRIBING INFORMATION WARNING: FATAL AND SERIOUS TOXICITIES: SEVERE DIARRHEA AND CARDIAC TOXICITIES Severe diarrhea occurred in 25% of FARYDAK treated patients. Monitor for symptoms, institute anti- diarrheal treatment, interrupt FARYDAK and then reduce dose or discontinue FARYDAK. (5.1) Severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes have occurred in patients receiving FARYDAK. Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at baseline and periodically during treatment as clinically indicated. (5.2) 1 INDICATIONS AND USAGE 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 [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing The recommended starting dose of FARYDAK is 20 mg, taken orally once every other day for 3 doses per week in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles. Consider continuing treatment for an additional 8 cycles for patients with clinical benefit who do not experience unresolved severe or medically significant toxicity. The total duration of treatment may be up to 16 cycles (48 weeks). FARYDAK is administered in combination with bortezomib and dexamethasone as shown in Table 1 and Table 2. The recommended dose of bortezomib is 1.3 mg/m2 given as an injection. The recommended dose of dexamethasone is 20 mg taken orally per scheduled day, on a full stomach. Table 1: Recommended Dosing Schedule of FARYDAK in Combination with Bortezomib and Dexamethasone During Cycles 1 to 8 21-Day Cycle Cycles 1 to 8 Week 1 Week 2 Week 3 (3-Week cycles) Days Days FARYDAK 1 3 5 8 10 12 Rest period Bortezomib 1 4 8 11 Rest period Dexamethasone 1 2 4 5 8 9 11 12 Rest period Table 2: Recommended Dosing Schedule of FARYDAK in Combination with Bortezomib and Dexamethasone During Cycles 9 to 16 21-Day Cycle Cycles 9 to 16 Week 1 Week 2 Week 3 (3-Week cycles) Days Days FARYDAK 1 3 5 8 10 12 Rest period Bortezomib 1 8 Rest period Dexamethasone 1 2 8 9 Rest period Reference ID: 3699607 2.2 Administration and Monitoring Instructions FARYDAK should be taken orally once on each scheduled day at about the same time, either with or without food [see Clinical Pharmacology (12.3)]. FARYDAK capsules should be swallowed whole with a cup of water. Do not open, crush, or chew the capsules [see How Supplied/Storage and Handling (16)]. If a dose is missed it can be taken up to 12 hours after the specified dose time. If vomiting occurs the patient should not repeat the dose, but should take the next usual scheduled dose. Counsel patients on the correct dosing schedule, technique of administration of FARYDAK, and when to take FARYDAK if dosing adjustments are made. Prior to the start of FARYDAK treatment and during treatment, monitoring should include: Complete Blood Count (CBC): Obtain a CBC before initiating treatment. Verify that the baseline platelet count is at least 100 x 109/L and the baseline absolute neutrophil count (ANC) is at least 1.5 x 109/L. Monitor the CBC weekly (or more often as clinically indicated) during treatment. [see Warnings and Precautions (5.4) Adverse Reactions (6.1)]. ECG: Perform an ECG prior to the start of therapy and repeat periodically during treatment as clinically indicated. Verify that the QTcF is less than 450 msec prior to initiation of treatment with FARYDAK. If during treatment with FARYDAK, the QTcF increases to ≥480 msec, interrupt treatment. Correct any electrolyte abnormalities. If QT prolongation does not resolve, permanently discontinue treatment with FARYDAK [see Warnings and Precautions (5.2), Adverse Reactions (6.1)]. During the clinical trial,