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]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Farydak Description FARYDAK (panobinostat lactate) is a histone deacetylase inhibitor. The chemical name of panobinostat lactate is 2-Hydroxypropanoic acid, compd. with 2-(E)-N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (1:1). The structural formula is: Panobinostat lactate anhydrous is a white to slightly yellowish or brownish powder. The molecular formula is C21H23N3O2?C3H6O3 (lactate); its molecular weight is 439.51 (as a lactate), equivalent to 349.43 (free base). Panobinostat lactate anhydrous is light sensitive. Panobinostat lactate anhydrous is both chemically and thermodynamically a stable crystalline form with no polymorphic behavior. Panobinostat free base is not chiral and shows no specific optical rotation. Panobinostat lactate anhydrous is slightly soluble in water. Solubility of panobinostat lactate anhydrous is pH-dependent, with the highest solubility in buffer pH 3.0 (citrate). FARYDAK capsules contain 10 mg, 15 mg, or 20 mg panobinostat free base. The inactive ingredients are magnesium stearate, mannitol, microcrystalline cellulose and pregelatinized starch. The capsules contain gelatin, FD&C Blue 1 (10 mg capsules), yellow iron oxide (10 mg and 15 mg capsules), red iron oxide (15 mg and 20 mg capsules) and titanium dioxide. FARYDAK capsules are packaged in PVC/PCTFE blister packs. Farydak(Panobinostat Lactate）临床用药方案 第一阶段治疗：第1－8个周期，每周期为3个星期（总时间为24周） •帕比司他:20mg口服，每日一次，每周三次，每周期使用两周休息一周。 •硼替佐米1.3mg/平米，每周两次静脉注射，每周期使用两周休息一周 •地塞米松20mg，口服，在用硼替佐米的当天和第二天 第二阶段治疗：第9－16个周期，每周期为3个星期（总时间为24周） 患者达到临床获益（评价标准为SD，PR，MR，nCR，或CR），没有严重的持续毒副反应，此时可考虑在修改剂量的基础上继续另外8个周期的治疗。 帕比司他:20mg口服，每日一次，每周三次，每周期使用两周休息一周。 •硼替佐米1.3 mg /平米，每周一次静脉注射，每周期使用两周休息一周 •地塞米松20 mg，口服，在用硼替佐米的当天和第二天。 注：以上中文资料仅供参考，使用以原处方为准：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7774972a-eeaa-4b9a-9e56-3fc1b968e86a FARYDAK capsules are packaged in PVC/PCTFE blister packs. 10mg blister packs containing 6 capsules………………………….……..NDC 0078-0650-06 15mg blister packs containing 6 capsules ………………………….…….NDC 0078-0651-06 20mg blister packs containing 6 capsules ………………………….…….NDC 0078-0652-06. Farydak (panobinostat, previously known as LBH589) is a histone deacetylase (HDAC) inhibitor indicated for the treatment of patients with multiple myeloma. The drug was discovered and developed by Novartis. In February 2015, Novartis received approval from US Food and Drug Administration (FDA) for Farydak in combination with bortezomib and dexamethasone for the treatment of multiple myeloma patients who previously received at least two regimens including bortezomib and an immunomodulatory (IMiD) agent. FARYDAK Rx 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 evaluated 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, itraconazole, ketoconazole, lopinavir/ritonavir, others); see Adults. Avoid star fruit, pomegranate or grapefruit juice. Avoid concomitant strong CYP3A inducers. Avoid concomitant sensitive CYP2D6 substrates (eg, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine) or substrates with narrow therapeutic index (eg, thioridazine, pimozide); if unavoidable, monitor frequently. Concomitant antiarrhythmics or QT prolonging drugs: not recommended. Antiemetics that prolong QT interval (eg, dolasetron, ondansetron, tropisetron): monitor ECG frequently. Adverse Reaction(s) Diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, vomiting, electrolyte imbalance, increased creatinine, thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemia. How Supplied: Blister packs—6 LAST UPDATED: 6/12/2015 诺华抗癌药Farydak获FDA批准，系首个治疗多发性骨髓瘤的HDAC抑制剂 2015年2月25日，瑞士制药巨头诺华（Novartis）的抗癌新药Farydak（panobinostat，LBH589）最终获得FDA青睐。FDA已批准Farydak联合Velcade（bortezomib，硼替佐米）和地塞米松（dexamethasone）用于既往接受至少2种治疗方案（包括Velcade和一种免疫调节（IMiD）药物）治疗失败的多发性骨髓瘤（myltiple myeloma，MM）患者群体。 FDA批准Farydak时附带有一项风险评估及减灾策略（REMS），用于宣传和教育医疗卫生专业人员了解可能与Farydak治疗相关的风险。 此次批准，也标志着Faryda成为用于治疗多发性骨髓瘤（MM）的首个组蛋白脱乙酰酶（HDAC）抑制剂，该药的表观遗传学活性，可能有助于恢复多发性骨髓瘤细胞的功能。 目前，Farydak在全球其他地区的监管审查正在进行中。 Farydak（panobinostat）是一种新型、广谱组蛋白脱乙酰酶（HDAC）抑制剂，具有一种新的作用机制，通过阻断组蛋白脱乙酰酶（HDAC）发挥作用，该药能够对癌细胞施以严重的应激直至其死亡，而健康细胞则不受影响。 Farydak通过FDA的加速审批程序批准。该药的获批是基于一项全球III期临床研究（PANORAMA-1）中一项预定义亚组分析（n=193）的疗效和安全性数据。数据显示，在既往接受硼替佐米和一种免疫调节（IMiD）药物治疗的多发性骨髓瘤（MM）群体中，联合标准治疗方案（硼替佐米+地塞米松）治疗时，与安慰剂（PFS=5.8个月，n=99）相比，Farydak延长了中位无进展生存期（PFS=10.6个月，n=94）。 此外，Farydak治疗组有59%的患者在治疗后肿瘤缩小或消失，而安慰剂组数据为41%。 不过，值得一提的是，Farydak的监管之路可谓波折。在2014年初，诺华提交panobinostat监管申请时，鉴于其良好的疗效，FDA表示将采用快速审批通道审核该药，使审查周期由通常的12个月缩短至8个月。 然而，去年11月底，FDA肿瘤药物顾问委员会（ODAC）以5:2的投票结果建议拒绝批准panobinostat。 该委员会表示，panobinostat针对经治多发性骨髓瘤（MM）患者群体确实有效，但该药的副作用过于严重，要求FDA慎重考虑。这一建议也迫使FDA将原定于12月份的最后期限推迟至今年3月。之后，诺华提交了额外的分析数据，同时修改panobinostat适应症，用于既往接受至少2种标准疗法（包括硼替佐米和免疫调节剂）的多发性骨髓瘤（MM）群体。FDA经过仔细审查后，最终批准panobinostat。需要指出的是，Farydak带有黑框警告，提示该药严重的腹泻和严重及致命的心脏事件、心律失常及心电图（ECG）变化。 多发性骨髓瘤（MM）是一种无法治愈且复发率很高的血液癌症。在过去的11年中，武田的抗癌药Velcade（硼替佐米）作为唯一一种已被证明能够延缓新诊和复发性多发性骨髓瘤（MM）总生存期（OS）的药物，在多发性骨髓瘤（MM）的临床治疗中发挥了重要作用。