部份中文瑞格非尼处方资料（仅供参考）
商品名：STIVARGA
英文名：Regorafenib
中文名：瑞格非尼薄膜衣片
成  份：Regorafenib
藥理類別：抗癌藥物
藥理類別 regorafenib
孕婦用藥分級 D 級：
在對照的人體研究試驗中顯示該藥物對胚胎有不良影響，若此藥能帶來之效益遠超過其它藥物的使用，因此即使在其危險性的存在下，仍可接受此藥物用於懷孕婦女上。
結構式
4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide hydrate
UpToDate UpToDate 連結 
藥理作用 
Regorafenib為多種膜上激酶及細胞內激酶的小分子抑制劑，這些激酶參與了正常的細胞功能也涉及許多病理進程，包括腫瘤發生、腫瘤血管新生以及維持腫瘤微環境。於體外的生化或細胞分析中，regorafenib或其人體內主要活性代謝物M-2及M-5在達到臨床給藥的濃度下會抑制RET、VEGFR1、VEGFR2、VEGFR3、KIT、PDGFR-alpha、PDGFR-beta、FGFR1、FGFR2、TIE2、DDR2、Trk2A、Eph2A、RAF-1、BRAF、BRAFV600E、SAPK2、PTK5及Ab1。於體內模式中，利用大鼠腫瘤證實regorafenib具抑制血管新生的效果，而利用多個小鼠異種移植模式(包括一些人類結腸直腸癌)，證實regorafenib可抑制腫瘤生長且具有抗腫瘤轉移效果。 
適應症 
1.1 大腸直腸癌
癌瑞格適用於治療先前曾接受下列療法的轉移性大腸直腸癌(mCRC)患者療法包含fluoropyrimidine-, oxaliplatin- 和 irinotecan- 為基礎的化療，和抗血管內皮生長因子(anti-VEGF)等療法；若KRAS為原生型(wild type)則須接受過抗表皮生長因子受體(anti-EGFR)療法。
1.2 腸胃道間質腫瘤
癌瑞格適用於治療先前曾接受imatinib mesylate與sunitinib malate治療的局部晚期、無法手術切除或轉移性的腸胃道間質腫瘤(GIST)患者。 
用法用量 
一個服藥週期為28天，建議劑量為每週期的前21天，每天口服160mg regorafenib 1次(四顆40mg藥錠)。持續接受治療直到病況惡化或發生無法接受的毒性。
每天同一時間服用癌瑞格。服用時請整顆吞下並配合脂肪含量低於30%的低脂早餐。低脂早餐的範例：兩片白吐司塗抹上1大匙低脂植物奶油及1大匙果醬，加上240毫升脫脂牛奶 (含319卡路里及8.2 g脂肪)；
或者1杯穀片、240毫升脫脂牛奶、1片塗抹果醬的吐司、蘋果汁以及1杯咖啡或茶(含520卡路里及2g脂肪)。 
藥動力學 
吸收
晚期實體腫瘤的病患單次使用癌瑞格160mg後，regorafenib於4小時的中位數時間，達幾何平均血中最高濃度(Cmax) 2.5μg/mL；血中濃度與時間曲線下面積(AUC)的幾何平均值為70.4μg*h/mL。
分佈
24小時的給藥間隔，可觀察到regorafenib經腸肝循環，產生多次最高血中濃度。Regorafenib與人類血漿蛋白具有高結合度(99.5%)。
代謝
Regorafenib經由CYP3A4以及UGT1A9進行代謝。於穩定狀態下，人類血漿
中測量到的regorafenib主要循環代謝物為M-2(N-oxide)和M-5(N-oxide和
N-desmethyl)，兩者與regorafenib有相似的體外藥理活性和穩定狀態濃度。M-2及M-5具高度的蛋白結合度(分別為99.8%和99.95%)。
排除
單次口服癌瑞格160mg，regorafenib和其M-2代謝物的血中排除半衰期的幾
何平均值分別為28小時(14至58小時)及25小時(14至32小時)。M-5具較長的
平均排除半衰期(範圍)，51小時(32至70小時)。
副作用 
最常出現的不良反應(≥20%)為全身無力/疲倦、
HFSR、腹瀉、食慾降低/食物攝取減少、高血壓、粘膜炎、發音異常、感染、疼痛(無特別指定何種疼痛)、體重減輕、胃腸道與腹部疼痛、皮疹、發燒與噁心。
接受癌瑞格治療的患者中，最嚴重的藥物不良反應為肝中毒、出血及胃腸道穿孔。 
禁忌 
無。 
給付規定 
9.51.Regorafenib（如Stivarga）：（104/9/1、105/8/1）
1.轉移性大腸直腸癌(mCRC)：
(1)用於治療先前曾接受下列療法的轉移性大腸直腸癌(mCRC)患者，療法包括fluoropyrimidine、oxaliplatin、irinotecan為基礎的化療，和抗血管內皮生長因子(anti-VEGF)等療法；若K-ras為原生型(wild type)，則需接受過抗表皮生長因子受體(anti-EGFR)療法。
(2)須經事前審查核准後使用，每次申請事前審查之療程以8週為限，再次申請必須提出客觀證據（如：影像學）證實無惡化，才可繼續使用。
2.胃腸道間質瘤(GIST) (105/8/1）
(1)先前曾接受imatinib 與sunitinib治療的局部晚期、無法切除或轉移性的胃腸道間質瘤患者。
(2)需經事前審查核准後使用，每次申請之療程以3個月為限，送審時需檢送影像資料，每3個月評估一次。
注意事項 
1. 肝毒性
癌瑞格開始治療前須進行肝功能檢測(ALT、AST及膽紅素)，且在治療的前2個月，至少每兩週要監測一次；接下來，每月至少須監測一次或依照臨床需要增加頻率。肝功能檢測數值升高的病患，須每週進行肝功能檢測，直到數值低於正常值上限/基期的三倍。
2. 出血
出現重度或危及生命的出血症狀的病患，請永久停用癌瑞格。接受warfarin的病患須更頻繁偵測其INR值。
3. 皮膚毒性
因皮膚毒性暫停使用癌瑞格後，降低劑量或永久停藥的決定取決於皮膚毒性的嚴重性及持續時間而定。進行支持性療法以緩解症狀。 
警語 
• 臨床試驗曾出現嚴重且可能致命的肝毒性現象。
• 在治療前及治療期間均需監測肝功能。
• 由肝功能檢測的數值上升程度及肝細胞壞死情形，可了解肝毒性的程度，再依據其嚴重程度及持續的時間來決定暫時停用癌瑞格，接下來應該降低藥量或終止使用癌瑞格。 
過量處理 
若疑似藥物過量，請停用癌瑞格、進行支持性療法，並持續觀察直到臨床跡象穩定。 
藥品保存方式 
儲存於30°C以下，運送時的允許溫度範圍為15至30°C (59至86°F)。
請將藥物儲存於原本的瓶子中，勿移除乾燥劑。首次開封後請鎖緊瓶蓋。
開瓶7週後，請將瓶中未使用的藥物丟棄。丟棄時請遵守當地規範。 
完整说明书附件：https://www.medicines.org.uk/emc/product/1263/smpc 。






INDICATIONS
STIVARGA® (regorafenib) is a prescription medicine used to treat people with:
•colon or rectal cancer that has spread to other parts of the body and for which they have received previous treatment with certain chemotherapy medicines
•a rare stomach, bowel, or esophagus cancer called GIST (gastrointestinal stromal tumor) that cannot be treated with surgery or that has spread to other parts of the body and for which they have received previous treatment with certain medicines
STIVARGA has not been used to treat children less than 18 years of age.
IMPORTANT SAFETY INFORMATION
STIVARGA can cause liver problems, which can be serious and sometimes lead to death. Your healthcare provider will do blood tests to check your liver function before you start taking STIVARGA and during your treatment with STIVARGA to check for liver problems. Tell your healthcare provider right away if you experience yellowing of your skin or the white part of your eyes, nausea, vomiting, dark urine, or change in your sleep pattern.
Before taking STIVARGA, tell your healthcare provider if you:
•have liver problems
•have bleeding problems
•have high blood pressure
•have heart problems or chest pain
•plan to have surgery
•have any other medical conditions
•are pregnant or plan to become pregnant. STIVARGA can harm your unborn baby. Females and males should use effective birth control during treatment with STIVARGA and for 2 months after their last dose of STIVARGA. Tell your healthcare provider right away if you or your partner becomes pregnant either while taking STIVARGA or within 2 months after your last dose of STIVARGA
•are breast-feeding or plan to breast-feed. It is not known if STIVARGA passes into your breast milk. You and your healthcare provider should decide if you will take STIVARGA or breast-feed
Tell your healthcare provider about all the prescription and nonprescription medicines, vitamins, and herbal supplements you take. Avoid drinking grapefruit juice and taking St. John's wort while taking STIVARGA.
STIVARGA may cause serious side effects, including:
•severe bleeding. STIVARGA can cause bleeding, which can be serious and sometimes lead to death. Tell your doctor if you have any signs of bleeding while taking STIVARGA, including: vomiting blood or if your vomit looks like coffee grounds, pink or brown urine, red or black (looks like tar) stools, coughing up blood or blood clots, menstrual bleeding that is heavier than normal, unusual vaginal bleeding, nosebleeds that happen often
•a skin problem called hand-foot skin reaction and severe skin rash. Hand-foot skin reaction causes redness, pain, blisters, bleeding, or swelling on the palms of your hands and soles of your feet (which may start as tingling). If you get this side effect or a severe skin rash, your healthcare provider may stop your treatment for some time
•high blood pressure. Your blood pressure should be checked regularly and any high blood pressure should be treated while you are receiving STIVARGA. Tell your healthcare provider if you have severe headaches, light-headedness, or changes in your vision
•decreased blood flow to the heart and heart attack. Get emergency help if you have chest pain, have shortness of breath, feel dizzy, or feel like passing out
•a condition called reversible posterior leukoencephalopathy syndrome (RPLS). Call your healthcare provider right away if you get severe headaches, seizure, confusion, change in vision, or problems thinking
•a tear in your stomach or intestinal wall (bowel perforation). STIVARGA may cause a tear in your stomach or bowel perforation that can be serious and sometimes lead to death. Contact your healthcare provider immediately if you notice severe pains or swelling in your stomach area (abdomen) or high fever
•wound healing problems. If you need to have a surgical procedure, tell your healthcare provider that you are taking STIVARGA. You should stop taking STIVARGA at least 2 weeks before any planned surgery
The most common side effects with STIVARGA include tiredness, weakness, fatigue; diarrhea (frequent or loose bowel movements); loss of appetite; swelling, pain, and redness of the lining in your mouth, throat, stomach, and bowel (mucositis); voice changes or hoarseness; infection; pain in other parts of your body; weight loss; and nausea.
Tell your doctor if you have any side effects that bother you or that do not go away.
For important risk and use information, please see the full Prescribing Information, including the Boxed Warning.