【佳學(xué)基因檢測(cè)】Odomzo (sonidegib)索尼德吉膠囊靶向用藥基因檢測(cè)

近日,美國食品和藥品監(jiān)督管理局(FDA)批準(zhǔn)Odomzo(sonidegib)治療有局部晚期基底細(xì)胞癌患者手術(shù)或放療后反復(fù)，或不是對(duì)手術(shù)或放療被選者。
皮膚癌是較常見癌而基底細(xì)胞癌約占非-黑色素瘤皮膚癌的80%。基底細(xì)胞癌開始在皮膚的頂層(被稱為表皮)和通常發(fā)生在曾被經(jīng)常暴露在陽光下和紫外輻射的其他形式的區(qū)域。按照美國國家癌癥研究所，非-黑色素瘤皮膚癌的新病例數(shù)似乎每年增加。局部地晚期基底細(xì)胞皮膚癌指基底癌尚未播散至機(jī)體其他部位，但不能用局部治療治好，特別是手術(shù)和輻射。
Odomzo是一種藥丸每天服用1次。它通過抑制一種分子途徑作用，被稱為刺猬信號(hào)通路[Hedgehog pathway]，在基底細(xì)胞癌中活化。通過抑制這個(gè)通路，Odomzo可能停止或減低癌性病變的生長(zhǎng)。
FDA的藥品評(píng)價(jià)和研究中心血液學(xué)和腫瘤室主任Richard Pazdur，M.D.說：“我們對(duì)涉及癌癥分子途徑了解的增加導(dǎo)致在難以治療疾病中許多腫瘤藥物的批準(zhǔn)其中少數(shù)治療選擇以前存在，” “感謝對(duì)刺猬信號(hào)通路的更好了解，只是在過去三年，F(xiàn)DA現(xiàn)已兩個(gè)藥物為基底細(xì)胞癌的治療。”在2012年，Erivedge(維莫德吉[vismodegib]是被批準(zhǔn)治療局部晚期和轉(zhuǎn)移基底細(xì)胞癌前列個(gè)藥物。
批準(zhǔn)日期：2015年7月24日[諾華]  2017年11月28日[太陽藥業(yè)]    公司：諾華制藥，太陽藥業(yè)
美國賊初批準(zhǔn)：2015年
警告：胚胎-胎兒毒性查看完整的盒裝警告的完整處方信息。
•當(dāng)給予孕婦時(shí)，ODOMZO可導(dǎo)致胚胎-胎兒死亡或嚴(yán)重的先天性缺陷，并且在動(dòng)物中具有胚胎毒性，胎兒毒性和致畸性。
•驗(yàn)證女性生育潛能的妊娠狀態(tài)，以便開始治療。建議具有生殖潛力的女性在用ODOMZO治療期間和賊后一次給藥后至少20個(gè)月使用有效的避孕措施。
•在使用ODOMZO治療期間至少8個(gè)月后，告知男性有可能通過精液暴露和與孕婦伴侶或生殖能力女性伴侶使用的潛在風(fēng)險(xiǎn)。
賊近的重大變化
警告和注意事項(xiàng)，皰疹的過早融合：05/2019
作用機(jī)制
Sonidegib是Hh途徑的抑制劑。Sonidegib結(jié)合并抑制Smoothened，一種涉及Hh信號(hào)轉(zhuǎn)導(dǎo)的跨膜蛋白。
適應(yīng)癥和用法
ODOMZO是一種hedgehog通路抑制劑，適用于治療患有局部晚期基底細(xì)胞癌（BCC）的患者，這些患者在手術(shù)或放射治療后發(fā)生，或者非手術(shù)或放射治療的患者。
劑量和給藥
建議劑量：每天口服200毫克，空腹，至少1小時(shí)或飯后2小時(shí)。
劑量形式和強(qiáng)度
200毫克膠囊
禁忌癥
沒有。
警告和注意事項(xiàng)
•胚胎-胎兒毒性：建議患者在使用ODOMZO治療期間以及在賊后一次給藥后至少20個(gè)月內(nèi)不捐獻(xiàn)血液或血液制品。
•肌肉骨骼不良反應(yīng)：在開始治療前，定期治療期間和臨床指征時(shí)獲得血清肌酸激酶（CK）和肌酐水平。根據(jù)肌肉骨骼不良反應(yīng)的嚴(yán)重程度，可能需要暫停劑量中斷或停止ODOMZO。
•骨骺過早融合。
不良反應(yīng)
在≥10％的患者中發(fā)生的賊常見的不良反應(yīng)是肌肉痙攣，脫發(fā)，味覺障礙，疲勞，惡心，肌肉骨骼疼痛，腹瀉，體重減輕，食欲減退，肌痛，腹痛，頭痛，疼痛，嘔吐和瘙癢。
要報(bào)告疑似不良反應(yīng)，請(qǐng)致電1-800-406-7984聯(lián)系SunPharmaceutical Industries，Inc?；蛑码?-800-FDA-1088或www.fda.gov/medwatch聯(lián)系FDA。
藥物相互作用
•CYP3A抑制劑：避免使用強(qiáng)效CYP3A抑制劑。避免長(zhǎng)期（超過14天）使用中度CYP3A抑制劑。
•CYP3A誘導(dǎo)劑：避免使用強(qiáng)效和中度CYP3A誘導(dǎo)劑。
用于特定人群
•哺乳期：建議不要母乳喂養(yǎng)。
包裝提供/存儲(chǔ)和處理
每個(gè)ODOMZO膠囊都有不透明的粉紅色，膠囊體上印有“SONIDEGIB 200MG”字樣，黑色墨水上印有“NVR”字樣。 ODOMZO膠囊供貨如下：
一瓶30粒NDC 47335-303-83
儲(chǔ)存在25°C（77°F）; 允許偏移15°C至30°C（59°F至86°F）[見USP受控室溫]。
完整說明資料附件：https://www.odomzo.com/themes/custom/odomzo/global/pdfs/pi.pdf
INDICATION
ODOMZO® (sonidegib) is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.
IMPORTANT SAFETY INFORMATION
WARNING: EMBRYO-FETAL TOXICITY
ODOMZO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. ODOMZO is embryotoxic, fetotoxic, and teratogenic in animals
Verify the pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential to use effective contraception during treatment with ODOMZO and for at least 20 months after the last dose
Advise males of the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with ODOMZO and for at least 8 months after the last dose
Embryo-fetal Toxicity: ODOMZO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman.
Females of Reproductive Potential: Verify pregnancy status prior to initiating ODOMZO. Advise females to use effective contraception and not to breastfeed, due to the potential for serious adverse reactions in breastfed infants, during treatment and for at least 20 months after the last dose. Based on animal studies, female fertility may be compromised. Report pregnancies to Sun Pharmaceutical Industries, Inc. at 1-800-406-7984.
Males: Advise males to use condoms, even after a vasectomy, and to not donate semen during treatment and for at least 8 months after the last dose to avoid potential drug exposure in pregnant females or females of reproductive potential.
Blood Donation: Advise patients not to donate blood or blood products while taking ODOMZO, and for at least 20 months after the last dose because their blood or blood products might be given to a female of reproductive potential.
Musculoskeletal Adverse Reactions: Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase (CK) elevations, occur with ODOMZO and other drugs which inhibit the hedgehog pathway. In a pooled safety analysis of 12 clinical studies involving 571 patients with various advanced cancers treated with ODOMZO, at doses ranging from 100 mg to 3000 mg, rhabdomyolysis (defined as serum CK increase of more than ten times the baseline value with a concurrent 1.5-fold or greater increase in serum creatinine above baseline value) occurred in 1 patient (0.2%) treated with ODOMZO 800 mg.
In Study 1, musculoskeletal adverse reactions occurred in 68% of patients treated with ODOMZO 200 mg daily, with 9% reported as Grade 3 or 4 serum CK elevations. The most frequent musculoskeletal manifestations reported were muscle spasms (54%), musculoskeletal pain (32%), and myalgia (19%). Increased serum CK laboratory values occurred in 61% of patients, with 8% having Grade 3 or 4. Musculoskeletal pain and myalgia usually preceded serum CK elevation. ODOMZO was temporarily interrupted in 8% of patients or permanently discontinued in 8% of patients for musculoskeletal adverse reactions. The incidence of musculoskeletal adverse reactions requiring medical intervention (magnesium supplementation, muscle relaxants, analgesics or narcotics) was 29%, including four patients (5%) who received intravenous hydration or were hospitalized.
Obtain baseline serum CK and creatinine levels prior to initiating ODOMZO, periodically during treatment, and as clinically indicated (eg, if muscle symptoms are reported). Obtain serum creatinine and CK levels at least weekly in patients with musculoskeletal adverse reactions with concurrent serum CK elevation greater than 2.5 times ULN until resolution of clinical signs and symptoms. Temporary dose interruption or discontinuation may be required. Advise patients starting ODOMZO of the risk of muscle-related adverse reactions and to promptly report any new unexplained muscle pain, tenderness, or weakness occurring during treatment or that persists after discontinuing ODOMZO.
Drug Interactions: Avoid concomitant administration of ODOMZO with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, administer for less than 14 days and monitor closely for adverse reactions, particularly musculoskeletal. Avoid concomitant administration of ODOMZO with strong and moderate CYP3A inducers.
Geriatric Use: There was a higher incidence of serious adverse events, Grade 3 and 4, and events requiring dose interruption or discontinuation in patients ≥65 years compared with younger patients; this was not attributable to an increase in any specific adverse event.
Most Common Adverse Reactions: The most common adverse reactions occurring in ≥10% of patients were muscle spasms (54%), alopecia (53%), dysgeusia (46%), fatigue (41%), nausea (39%), musculoskeletal pain (32%), diarrhea (32%), decreased weight (30%), decreased appetite (23%), myalgia (19%), abdominal pain (18%), headache (15%), pain (14%), vomiting (11%), and pruritus (10%).