2009054860輔美康注射劑80毫克 衛署藥輸字第025882號FIRMAGON® 80 mg Powder and Solvent for Solution for Injection輔美康注射劑 120毫克 衛署藥輸字第025883號FIRMAGON® 120 mg Powder and Solvent for Solution for Injection本藥限由醫師使用

［劑型］注射用凍晶乾粉及溶劑。

［成份］80 mg每小瓶凍晶乾粉含80mg degarelix，溶解後每毫升溶液含有20mg degarelix。120 mg每小瓶凍晶乾粉含120mg degarelix，溶解後每毫升溶液含有40mg degarelix。本品所含賦形劑之成分請詳見［賦形劑］。

［藥品性狀］粉劑：白色至類白色粉末。

溶劑：透明無色溶液。［適應症］成年男性晚期荷爾蒙依賴型前列腺癌。

［用法用量］劑量：初始劑量 維持劑量（每月一次）240mg，皮下注射兩次，每次120mg 80mg，皮下注射一次

第一次維持劑量應在初始劑量1個月後開始。FIRMAGON® 的治療效果應經過檢測臨床指標和血清前列腺特異抗原(PSA)來評估。臨床研究顯示，初始劑量注射後立刻發生睪固酮抑制，96%的病人在初始劑量注射後 3天，100%的病人在初始劑量注射後1個月，血清睪固酮達藥物去勢濃度（T≤0.5ng/ml）。 長期以維持劑量治療達1年後顯示，97%的病人維持在睪固酮抑制濃度（T≤0.5ng/ml）。在臨床效果不太理想的病人，應確認血清睪固酮濃度維持在充分抑制濃度。因為FIRMAGON®不會導致睪固酮濃度激增，所以初始治療時不需要併用抗雄性激素藥物以抑制睪固酮激增。注射方法：FIRMAGON®僅用於皮下注射，不可靜脈注射。不推薦肌肉注射，因為無相關研究。FIRMAGON®　用於腹部皮下注射。與其他皮下注射的藥物一樣，注射區域應該作週期性更改，應選擇無外在壓力的區域，不適合靠近腰帶和束帶，也不應靠近肋骨。本品配置步驟需仔細遵照說明，詳見［使用及棄置說明］。不建議注射其他濃度。配置後溶液應為沒有不溶物質之清澈液體。特殊族群之劑量調整：老年人、肝或腎功能不全之患者對於老年病人、輕度至中度的肝或腎功能不全的病人，無需調整劑量（詳見［藥物動力學特性］）。對於嚴重肝或腎功能不全的病人，建議審慎使用，因為無相關研究。本品無相關適應症用於女性、兒童和青少年。

［禁忌］對FIRMAGON® 的活性成份或賦型劑過敏者禁用。懷孕分類等級X。Degarelix禁用於懷孕或可能懷孕的婦女。投與degarelix於懷孕婦女會對胎兒產生傷害。以體表面積(mg/m2)為基礎，投與degarelix臨床上初始劑量(240mg)的0.02%會導致器官形成期的兔子胚胎和胎兒死亡及流產。以體表面積(mg/m2)為基礎 ，對器官形成期的懷孕雌性大鼠投與degarelix臨床上初始劑量的0.036%，會導致胚胎著床後流產增加和降低活胎數。假如這個藥品用於懷孕期間或假如病患在用藥期間懷孕，需要先告知病患藥物對胎兒的潛在影響。

［注意事項］對心電圖QT/QTc interval的影響：雄激素阻斷治療可能會延長QT interval。醫師須審慎評估是否對於先天性QT延長、充血性心衰竭、經常性電解質異常和正在服用已知會延長QT interval 藥物之患者，使用雄激素阻斷治療之利益是否大於可能存在之風險。如有電解質異常應矯正。可考慮使用心電圖及電解質進行週期性的監測。肝功能不全：已知或懷疑肝功能不全的病人未包括在長期應用degarelix的臨床試驗中。可見輕度和短暫的ALT和AST升高，但都不伴有膽紅素升高和臨床症狀。對於已知或懷疑肝功能不全患者，建議在治療過程中檢測肝功能。已做輕度至中度肝功能不全患者單次靜脈注射後的degarelix的藥物動力學的相關研究。（詳見［藥物動力學特性］）腎功能不全：尚無degarelix 應用於嚴重腎功能不全的病人的相關研究，因此應慎用於嚴重腎功能不全患者。葡萄糖耐受性：在曾接受去勢手術或促性腺激素釋放激素促效劑（GnRH agonist）治療的男性患者中可觀察到葡萄糖耐受性減低，可能發生糖尿病的發展或惡化，因此糖尿病的病人在接受雄激素阻斷治療時可能需要更頻繁檢測血糖濃度。尚無相關degarelix對於胰島素和血糖濃度影響的研究。

［藥物交互作用］尚未進行藥物交互作用的相關研究。因雄性激素阻斷治療可能使心電圖QTc interval 延長，使用degarelix時如伴隨其他已知導致QTc interval 延長或誘導Torsades de Pointes的藥物應謹慎評估。例如抗心律不整藥物IA類（如：quinidine, disopyramide）和III類（如amiodarone, sotalol, dofetilide, ibutilide）抗心律不整藥品、methadone、 cisapride、moxifloxacin、抗精神病藥等應該小心評估（詳見［注意事項］）。Degarelix 不是人類CYP450系統的受質，並沒有證據顯示在體外會大量誘導或抑制CYP1A2、CYP2B6, CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP2E1或CYP3A4/5的變化。因此在臨床上未必有顯著藥物間的藥物動力學交互作用。

［生殖、妊娠和授乳］FIRMAGON®禁止使用於懷孕婦女，詳見［禁忌］。

［駕駛和操作機器］尚無FIRMAGON®　對於駕駛和操作機器能力影響的相關研究。

［不良反應］在III期臨床研究中，使用FIRMAGON®　治療最常見的不良反應是由於睪固酮抑制導致的生理學變化，包括潮熱和體重增加（在接受治療1年時間內，報告分別有25%和7%），及注射部位的副作用。注射後數小時偶爾有短暫的寒顫、發熱或類流感疾病的報導（分別佔3%、2%和1%）。注射部位的不良反應主要是疼痛和紅斑，分別佔病例數的28%和17%。較少出現的不良反應有腫脹（6%）、硬結（4%）和結節（3%）。這些通常發生在初始劑量治療時。而以維持劑量治療時，這些反應的發生率為：每100次注射中，有3次疼痛，少於1次的紅斑、腫脹、結節和硬結。這些不良反應大多數是短暫及屬輕度至中度強度，並且很少導致治療中斷（<1%）。嚴重性注射部位不良反應非常少發生，如注射部位感染、注射部位膿腫或可能需要執行手術治療/引流之注射部位壞死。下表中不良反應發生率的定義為：很常見（≥1/10）；常見（≥1/100且<1/10）；不常見（≥1/1000且<1/100）；罕見 (≥1/10000且<1/1000)。表1：不良反應報告頻率MedDRA系統 器官類別（SOC） 很常見 常見 不常見 罕見

血液及淋巴系統失調

貧血* 嗜中性白血球低下發燒

免疫系統失調 過敏反應 過敏性反應

代謝和營養失調 體重增加*

高血糖症/糖尿病、膽固醇升高、體重降低、食慾下降、血鈣改變

精神功能失調 失眠 憂鬱症、性慾降低＊

神經系統失調 眩暈、頭痛 精神損害、觸覺減退

視力障礙 視力模糊

心臟功能失調

心律不整(包括心房顫動)、心悸、QT interval 延長＊（詳見［注意事項］和［藥物交互作用］）

心肌梗塞、心臟衰竭

血管系統失調 潮熱＊高血壓、血管迷走神經反應(包括低血壓)

呼吸、胸廓和縱隔失調 呼吸困難

胃腸道失調 腹瀉、噁心 便秘、嘔吐、腹痛、腹部不適、口乾

肝臟和膽管失調 肝轉氨酶升高 膽紅素增加、鹼性磷酸酶增加

皮膚和皮下組織失調

多汗＊（包括夜間盜汗*）、皮疹

蕁麻疹、皮膚結節、脫髮、搔癢、紅斑

骨骼肌肉、結締組織和骨骼失調

肌肉骨骼痛和不適

骨質疏鬆/骨量減少、關節肌肉無力、肌肉痙癴、關節腫脹/ 強直

腎與泌尿系統失調頻尿、尿急、排尿困難、夜尿症、腎功能不全、尿失禁

生殖系統和乳腺失調

男性女乳症*、睪丸萎縮*、勃起障礙*

睪丸疼痛、乳房痛、骨盆痛、生殖器刺激、射精失敗

一般症狀和給藥部位異常

注射位置不良反應

寒顫、發熱、疲勞＊、類流感症狀

全身乏力、局部水腫

*睪固酮抑制所產生的生理性反應

過敏反應:FIRMAGON®上市後曾被報導出有過敏反應，包括過敏性反應、蕁麻疹和血管性水腫。骨密度改變:有醫學期刊指出，進行睪丸切除術之男性患者或以促性腺激素釋放激素促效劑 (GnRH agonist) 治療之患者，其骨密度會減少。可預期長期接受雄激素阻斷治療之男性患者其骨密度將會受到影響。

［過量］目前尚無應用FIRMAGON® 急性過量的臨床經驗。在藥物過量的事件中，應監測病人的情況和在必要時給予合適的支持治療。

［藥效動力學特性］藥理治療分類：內分泌療法，其他荷爾蒙拮抗劑和相關製劑，ATC碼：L02BX02。作用機轉Degarelix是一種選擇性促性腺激素釋放激素阻斷劑 (GnRH blocker)，它可以競爭的及可逆的與腦下垂體的促性腺激素釋放激素(GnRH)受體結合，迅速的降低促性腺激素、黃體激素 (LH) 和濾泡激素 (FSH) 釋放，從而減少睪丸分泌睪固酮（T）。已知前列腺癌對雄激素敏感，並對雄性激素阻斷治療有良好反應。不像促性腺激素釋放激素受體促效劑(GnRH agonists)，促性腺激素釋放激素受體阻斷劑(GnRH receptor blockers)在初始治療後不會出現促黃體激素的激增而導致睪固酮激增/腫瘤進展和加重潛在的症狀。初始劑量FIRMAGON®　 240mg和接著以每月80mg維持劑量，可以迅速降低黃體激素（LH）、濾泡激素（FSH）和睪固酮（T）的濃度。血清雙氫睪固酮（DHT）的濃度降低類似於睪固酮。FIRMAGON®能有效達到和維持睪固酮良好的抑制濃度到藥物去勢濃度0.5ng/ml以下。每月維持劑量80mg就可以使97%的病人在1年內維持睪固酮抑制濃度。經過1年的維持治療，睪固酮濃度的中位數是0.087ng/ml（範圍0.06‑0.15，N=167）。

圖1、服用degarelix 240mg/80mg第0至364天之血中睪固酮濃度 (中位數與間距範圍)III期臨床試驗的結果：FIRMAGON®的療效和安全性的研究是一個開放性、多中心、隨機、平行對照的臨床研究。該研究採用FIRMAGON®兩種不同的每月劑量，對患前列腺癌和需要雄性激素阻斷的病人給予初始劑量240mg（40mg/ml）後，分別於每月皮下注射維持劑量160mg（40mg/ml）或者80mg（20mg/ml），對照組則以肌肉注射leuprorelin 7.5mg作研究。總數620位病人被隨機分到三組治療組中的其中一組。接受隨機治療的610位病人中：31%局部型前列腺癌；29%局部晚期性前列腺癌；20%轉移性前列腺癌；7% 未知轉移狀態的前列腺癌；13%是曾接受治癒性手術治療或放射治療後，而PSA再次升高。人口統計學基數顯示各組基準相同，年齡中位數74歲（範圍47至98歲）。研究的主要目的是證明degarelix能在12個月的治療過程中有效達到和維持睪固酮抑制濃度少於0.5 ng/ml。研究採用最低有效維持劑量80mg degarelix。研究的主要目的是證明FIRMAGON®　能在12個月的治療過程中有效達到和維持睪固酮抑制濃度少於0.5ng/ml。總數620位病人被隨機分到三組治療組中的其中一組，共有504位病人（81%）完成該項試驗。在degarelix 240/80mg治療組中有41位病人

（20%）未完成全部研究，而leuprorelin組中則有32位病人（16%）中止試驗。達到血清睪固酮抑制（T≤ 0.5ng/ml）：FIRMAGON®　能有效地達到快速睪固酮抑制，詳見表2。表2：初始劑量後病人達至血清睪固酮抑制（T≤ 0.5ng/ml）的百分數時間 FIRMAGON®　 240/80mg s.c. Leuprorelin 7.5mg i.m.第1天 52% 0%第3天 96% 0%第7天 99% 1%第14天 100% 18%第28天 100% 100%避免睪固酮激增：使用degarelix治療的病人中沒有出現睪固酮激增，在用藥第三天睪固酮濃度平均降低94%。大部分應用leuprorelin治療的病人出現睪固酮激增，在用藥第三天睪固酮濃度平均升高65%。睪固酮激增的定義為在初始2周內血清睪固酮含量上升超過基準 ≥15%。兩組的數據有顯著的差異（p<0.001）。

圖2：用藥28天內血清睪固酮偏離基線的變化（中位數與間距範圍）本研究的主要療效指標是使用degarelix或leuprorelin治療1年後睪固酮抑制的比率。該療效指標的比較，並無法顯示在治療初期degarelix 不須如同leuprorelin治療要加上抗雄性激素藥物臨床優勢。睪固酮可逆性有一項研究納入病患接受局部治療後 (主要為放射性前列腺切除術及放射治療) 前列腺特異性抗原 (PSA) 增加之患者，讓其服用FIRMAGON®七個月並進行七個月之監測。停止治療後，達到睪固酮回復 (>0.5 ng/ml，去勢濃度以上) 之中位數為112天 (從起始監測開始計算，例如最近一次注射後的28天)。達到睪固酮>1.5 ng/ml (正常範圍最低限度以上) 之中位數為168天。長期效果：該研究中有效反應定義為，28天內達到藥物去勢濃度，並且在364天內維持在去勢濃度而睪固酮濃度不超過0.5ng/ml。表3：用藥28至364天睪固酮濃度≤0.5ng/ml的累積概率

FIRMAGON® 240/80mg

N=207

Leuprorelin 7.5mgN=201

有效反應的病例數 202 194有效率＊（可信區間） 97.2%（93.5; 98.8%） 96.4%（92.5; 98.2%）

＊組間Kaplan meier檢驗達到前列腺特異性抗原（PSA）的減少：臨床試驗中未直接測量腫瘤大小的變化，但前列腺特異抗原PSA濃度的中位數在12個月內下降95%的數據資料，可間接顯示對腫瘤有效反應的臨床益處。研究中PSA濃度的中位數：使用FIRMAGON®治療群組，19.8ng/ml（間距範圍為P25 9.4ng/ml，P75 46.4ng/ml)。使用leuprorelin7.5mg群組，17.4ng/ml（間距範圍為P25 8.4ng/ml，P75 56.5ng/ml)

圖3：治療56天PSA距離基線濃度的變化百分率（中位數與間距範圍）在用藥14天和28天，兩組的數據有顯著的差異（p<0.001）。前列腺特異抗原（PSA）濃度在注射FIRMAGON® 兩周後下降64%，1月後下降85%， 3月後下降95%，並且在一年治療期間睪固酮抑制濃度維持在大約97%。在用藥56天至364天，使用FIRMAGON®群組和使用leuprorelin群組距離基線變化沒有顯著差異。前列腺體積之影響以degarelix (240/80 mg 劑量) 治療原本需以荷爾蒙治療優先於放射性治療，或為藥物去勢之後補之患者三個月後，經直腸超音波 (TRU) 測量顯示前列腺體積減少37%。前列腺體積減少相似於接受goserelin加上抗雄性激素之保護作用。QT/QTc interval之影響在對比FIRMAGON®和leuprolide的隨機控制臨床研究中，進行了週期性心電圖檢查。使用degarelix群組的7位病人中，有3位 (<1%) 的QTcF≥500毫秒；使用

leuprolide 7.5 毫克群組的病人則有4 (2%) 位。從基礎值到研究結束，使用FIRMAGON® 群組的變化中位數是12.3毫秒，而使用leuprolide群組的變化中位數是16.7毫秒。一項QT研究顯示，degarelix對於QT/QTc interval無本質上的影響。由健康男性 (N=80) 接受靜脈注射degarelix超過60分鐘，確認degarelix對於心臟再極化 (QTcF)、心跳、AV傳導、心臟去極化、或T或U波形無影響，其Cmax達到中間值222 ng/ml，約為接受前列腺癌治療患者之Cmax的3‑4倍。抗degarelix抗體使用FIRMAGON®　治療1年後，有10%的病人出現了degarelix的抗體；有29%的病人使用FIRMAGON®　治療超過5.5年後出現抗體。沒有證據顯示使用FIRMAGON® 治療超過5.5年後其有效性和安全性受到抗體的影響。

［藥物動力學特性］注射溶液之濃度對於藥物動力學影響很大。因此，除了建議劑量濃度外，不應使用其他劑量。

吸收：在 樞 紐 試 驗 C S 2 1 研 究 中 ，前 列 腺 癌 的 病 人 接 受 皮 下 注 射 濃 度 為 40mg/ml的 degarelix 240mg後，血中濃度 AUC0‑28 days為635（602‑668）天*ng/ml，最高藥物血中濃度Cmax為 66.0（61.0‑71.0）ng/ml，到達最高血中濃度時間tmax發生在40

（37‑42）小時。平均波谷濃度在使用初始劑量後大約為11‑12ng/ml，在使用維持劑量為80mg（濃度20mg/ml）後為11‑16 ng/ml。Degarelix最高血中濃度以二相性形式被清除，其維持劑量的平均半衰期 (t1/2) 為29天。皮下注射後的半衰期較長是由於degarelix會在注射部位緩慢釋放。藥品的藥物動力學行為受到注射時藥物濃度的影響。最高血中濃度和生體可用率會隨著藥物濃度增加而減少，其半衰期則會增加。因此，除了建議劑量濃度外，不應使用其他劑量。前列腺癌的病人接受皮下注射濃度為40mg/ml的FIRMAGON®240mg後， Degarelix以二相性形式被清除，估計初始劑量FIRMAGON® 240 mg (濃度40 mg/ml)的半衰期

（t1/2）中位數大約為43天，維持劑量FIRMAGON® 80 mg (濃度20 mg/ml) 的半衰期中位數大約為28天。皮下注射後較長的半衰期是由於degarelix會在注射部位緩慢釋放。藥品的藥物動力學行為受到注射時藥物濃度的影響。分佈：在健康老年男性體內的分佈體積大約為1 L/Kg，血清蛋白結合率大約為90%。代謝：Degarelix通過肝膽系統時經一般胜肽類降解，主要降解為肽類殘餘物由糞便排泄。皮下注射後在血漿樣本中沒有觀察到明顯的代謝物。體外研究顯示，degarelix不是人體CYP450系統的受質。排除：在健康男性中大約20‑30%的degarelix藥物劑量會經由尿液排除，顯示將近70‑80%在人體中經由肝膽系統排泄。健康年老男性的清除率為35‑50ml/h/kg。特殊族群：腎功能不全患者：尚未執行腎功能不全病人的藥物動力學研究。服用本品後只有相當於給藥劑量的20%的原型degarelix由腎臟排出。從III期確認臨床試驗群體藥動學研究分析中顯示，輕度至中度的腎功能不全患者中degarelix的清除率會下降20‑30%，因此不建議對輕度至中度腎功能不全患者進行劑量調整。重度腎功能不全患者的資料很少，因此應慎用於這些類型的患者。肝功能不全患者：已執行degarelix對於輕度至中度的肝功能不全患者的藥物動力學研究。相對健康受試者未發現肝功能不全患者暴露量的升高。不需要對輕度至中度肝功能不全患者進行劑量調整。未有對重度肝功能不全患者的研究，因此應慎用於這些患者。老年患者:參與FIRMAGON®臨床試驗的受試者中，82 %為65歲以上，42%為75以上。整體來說，這些受試者的安全性及有效性與較年輕受試者並沒有差異，但無法排除有些較年長的個體有較高的敏感度。

［臨床前的安全性資料］對動物生殖系統的研究顯示，degarelix可以導致雄性動物不育，這是由於藥理學的效果，且這種影響是可逆轉的。對於雌性生殖系統的毒性研究顯示了預期的degarelix藥理學的特性。其可以導致劑量依賴性的交配和懷孕時間延長，黃體數目減少，增加著床前後失敗、流產、早期胚胎/胎兒死亡、早產、分娩期間延長的機會。關於藥理安全性、重複劑量毒性、基因毒性、致癌可能性的臨床前研究數據顯示，未發現對人類有害的影響。在給大鼠和猴子皮下注射degarelix後的急性、亞急性和慢性毒性研究中，沒有發現標靶器官毒性。給予動物皮下注射高劑量的degarelix後，可以觀察到藥物相關的局部刺激反應。

［賦形劑］Mannitol (E421), Water for Injection

［配伍禁忌］尚無配伍禁忌方面的研究，本品不能與其他藥品混合在一起。

［有效期間］詳見外包裝。配製後 (詳見［使用及棄置說明］) 應立即使用。加入溶劑後，配置好的溶液其化學和物理穩定性在25oC環境下可以維持2小時。 從微生物學角度，一旦本品配置好後應立即使用。

［貯存注意事項］貯存於30oC以下。不可冷凍。關於配置後溶液之儲存條件詳見［有效期間］。

［包裝］80 mg玻璃小瓶(type I)帶有橡膠瓶塞和鋁翻蓋密封，含有80毫克凍晶乾粉預充填玻璃注射針筒(type I)，推筒塞、頂蓋、針筒4ml處有一條標記，含4.2毫升的溶劑推筒小瓶接合器注射用針頭（25G 0.5×25mm）包裝規格:1個包裝含有1瓶裝有凍晶乾粉之玻璃小瓶、1支預充填玻璃注射針筒、1個推筒、1個小瓶接合器及1個注射用針頭。120 mg玻璃小瓶(type I)帶有橡膠瓶塞和鋁翻蓋密封，含有120毫克凍晶乾粉預充填玻璃注射針筒(type I)，推筒塞、頂蓋、針筒3ml處有一條標記，含3毫升的溶劑推筒小瓶接合器注射用針頭（25G 0.5×25mm）包裝規格:1個包裝含有2瓶裝有凍晶乾粉之玻璃小瓶、2支預充填玻璃注射針筒、2個推筒、2個小瓶接合器及2個注射用針頭。

［使用及棄置說明］：必須按照以下步驟進行配製。不推薦使用其他濃度，因為凝膠形態受濃度影響。配製後的溶液應為透明液體，無不溶物質。注意：不可搖晃藥瓶80 mg包裝中含有1套用於皮下注射的凍晶乾粉和預充填針筒的溶劑。

1. 拿掉小瓶接合器的套子。將小瓶接合器裝在乾粉的小瓶上，然後將接合器壓下直到針穿刺過橡皮塞且緊密接合。

2. 準備預充填針筒裝上推筒。

3. 拿掉預充填針筒的頂蓋。將針筒接上乾粉小瓶並旋入接合器。將所有的溶劑打入乾粉小瓶。

4. 針筒仍然連結於接合器上輕輕的旋轉直到液體澄清沒有尚未溶解的乾粉或粒子。假如粉末黏在高過液面的小瓶上，可以將瓶子稍微的傾斜。避免搖晃以預防氣泡產生。 環狀的小氣泡在液體表面是可以接受的。混合的過程通常只要幾分鐘就可以，但有些也許需要超過15分鐘。

5. 將小瓶上下顛倒，抽取溶液到達針筒的標記，用於注射。必須確認抽出精確的體積及移除任何氣泡。

6. 將針筒與接合器分開，然後針筒接上深部皮下注射針。

7. 執行深部皮下注射。抓住腹部皮膚，抬起皮下組織，以進針角度不小於45度角進行深部皮下注射。緩慢的注射4 ml 的FIRMAGON® 80 mg，在配置好後立刻注射*。

8. 注射區域不應該選擇有外在壓力的區域，不適合靠近腰帶和束帶，也不應靠近肋骨。

不可注射入靜脈。輕輕回抽以確認沒有回血。如果血液在注射器出現，藥品則不能使用。終止操作，並丟棄注射器和針頭（為病人配製一份新的藥品）。

120 mg包裝中含有2套用於皮下注射的凍晶乾粉和預充填針筒的溶劑。因此以下所描述的步驟需要重複做2次。

1. 拿掉小瓶接合器的套子。將小瓶接合器裝在乾粉的小瓶上，然後將接合器壓下直到針穿刺過橡皮塞且緊密接合。

2. 準備預充填針筒裝上推筒。

3. 拿掉預充填針筒的頂蓋。將針筒接上乾粉小瓶並旋入接合器。將所有的溶劑打入乾粉小瓶。

4. 針筒仍然連結於接合器上輕輕的旋轉直到液體澄清沒有尚未溶解的乾粉或粒子。假如粉末黏在高過液面的小瓶上，可以將瓶子稍微的傾斜。避免搖晃以預防氣泡產生。環狀的小氣泡在液體表面是可以接受的。混合的過程通常只要幾分鐘就可以，但有些也許需要超過15分鐘。

5. 將小瓶上下顛倒，抽取溶液到達針筒的標記，用於注射。必須確認抽出精確的體積及移除任何氣泡。

6. 將針筒與接合器分開，然後針筒接上深部皮下注射針。

7. 執行深部皮下注射。抓住腹部皮膚，抬起皮下組織，以進針角度不小於45度角進行深部皮下注射。

緩慢的注射3 ml 的FIRMAGON® 120 mg，在配置好後立刻注射*。

8. 注射區域不應該選擇有外在壓力的區域，不適合靠近腰帶和束帶，也不應靠近肋骨。不可注射入靜脈。輕輕回抽以確認沒有回血。如果血液在注射器出現，藥品則不能使用。終止操作，並丟棄注射器和針頭（為病人配製一份新的藥品）。

9. 第二劑重複同樣的配製過程，選擇第二個不同的注射部位，並注射3 ml藥品。

*在25℃環境下化學和物理穩定性可以維持2小時。從微生物學角度，除非配製方法可排除微生物感染的風險，否則藥品應立即使用；如果不立即使用，貯藏的時間和條件均屬使用者的責任。本品沒有特殊棄置要求。

凍晶乾粉及溶劑製造廠：Ferring GmbHWittland 11, D‑24109 Kiel, Germany包裝廠：Ferring International Center SAChemin de la Vergognausaz 50,1162 Saint‑Prex, Switzerland

藥商：輝凌藥品股份有限公司地址：台北市松江路111號11樓電話：(02) 25158277

FIRMAGON® 80 mgFIRMAGON® 120 mg

PHARMACEUTICAL DOSAGE FORMPowder and solvent for solution for injection

QUALITATIVE AND QUANTITATIVE COMPOSITION80 mgEach vial contains 80 mg degarelix (as acetate). After reconstitution each ml of solution contains 20 mg of degarelix.120 mgEach vial contains 120 mg degarelix (as acetate). After reconstitution each ml of solution contains 40 mg of degarelix.

For the full list of excipients, see section LIST OF EXCIPIENTS.

PHARMACEUTICAL FORMPowder: White to off‑white powderSolvent: Clear, colorless solution

THERAPEUTIC INDICATIONSFIRMAGON® is a gonadotrophin releasing hormone (GnRH) receptor blocker indicated for treatment of adult male patients with advanced hormone‑dependent prostate cancer.

POSOLOGY AND ADMINISTRATIONPosology

Starting dose Maintenance dose – monthly administration

240 mg administered as two subcutaneous injections of 120 mg each

80 mg administered as one subcutaneous injection

The first maintenance dose should be given one month after the starting dose.

The therapeutic effect of degarelix should be monitored by clinical parameters and prostate specific antigen (PSA) serum levels. Clinical studies have shown that testosterone (T) suppression occurs immediately after administration of the starting dose with 96% of the patients having serum testosterone levels corresponding to medical castration (T≤0.5 ng/ml) after three days and 100% after one month. Long term treatment with the maintenance dose up to 1 year shows that 97% of the patients have sustained suppressed testosterone levels (T≤0.5 ng/ml).

In case the patient’s clinical response appears to be sub‑optimal, it should be confirmed that serum testosterone levels are remaining sufficiently suppressed.

Since FIRMAGON® does not induce a testosterone surge it is not necessary to add an anti‑androgen as surge protection at initiation of therapy.

Method of administrationFIRMAGON® is for subcutaneous administration only and is not to be administered intravenously. Intramuscular administration is not recommended as it has not been studied.FIRMAGON® is administered as a subcutaneous injection in the abdominal region. As with other drugs administered by subcutaneous injection, the injection site should vary periodically. Injections should be given in areas where the patient will not be exposed to pressure e.g. not close to waistband or belt and not close to the ribs.

The reconstitution procedure needs to be carefully followed, see instructions in Section Special precautions for disposal and other handling. Administration of other concentrations is not recommended. The reconstituted solution should be a clear liquid, free of undissolved matter.

Dose adjustment in special patient populationsElderly, Hepatically or Renally impaired:There is no need to adjust the dose for the elderly or in patients with mild or moderate liver or kidney function impairment (see section Pharmacokinetics properties). Patients with severe liver or kidney dysfunction have not been studied and caution is therefore warranted. There is no relevant indication for FIRMAGON® in women, children and adolescents.

CONTRAINDICATIONSHypersensitivity to the active substance or to any of the excipients.Pregnancy Category X:Degarelix is contraindicated in women who are or may become pregnant. Degarelix can cause fetal harm when administered to a pregnant woman. Degarelix given to rabbits during organogenesis at doses that were 0.02% of the clinical loading dose (240 mg) on a mg/m2 basis caused embryo/fetal lethality and abortion. When degarelix was given to female rats during organogenesis, at doses that were just 0.036% of the clinical loading dose on a mg/m2 basis, there was an increase post implantation loss and a decrease in the number of live fetuses. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

SPECIAL WARNINGS AND PRECAUTIONS FOR USEEffect on QT/QTc intervalAndrogen deprivation therapy may prolong the QT interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Hepatic impairmentPatients with known or suspected hepatic disorder have not been included in long‑term clinical trials with degarelix. Mild, transient increases in ALT and AST have been seen, these were not accompanied by a rise in bilirubin or clinical symptoms. Monitoring of liver function in patients with known or suspected hepatic disorder is advised during treatment. The pharmacokinetics of degarelix has been investigated after single intravenous administration in subjects with mild to moderate hepatic impairment (see section PHARMACOKINETICS PROPERTIES).

Renal impairmentDegarelix has not been studied in patients with severe renal impairment and caution is therefore warranted.

Glucose toleranceA reduction in glucose tolerance has been observed in men who have had orchiectomy or who have been treated with a GnRH agonist. Development or aggravation of diabetes may occur; therefore diabetic patients may require more frequent monitoring of blood glucose when receiving androgen deprivation therapy. The effect of degarelix on insulin and glucose levels has not been studied.

INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTIONNo drug‑drug interaction studies have been performed.Since androgen deprivation treatment may prolong the QTc interval, the concomitant use of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, cisapride, moxifloxacine, antipsychotics, etc. should be carefully evaluated (see section Special Warnings and Precautions for Use).Degarelix is not a substrate for the human CYP450 system and has not been shown to induce or inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 to any great extent in vitro. Therefore, clinically significant pharmacokinetic drug‑drug interactions are unlikely.

FERTILITY, PREGNANCY AND LACTATIONFIRMAGON® must not be used in pregnant women, see section Contraindications.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINESNo studies on the effects of FIRMAGON® on the ability to drive and use machines have been performed.

UNDESIRABLE EFFECTSThe most commonly observed adverse reactions during FIRMAGON® therapy in the confirmatory phase III study were due to the expected physiological effects of testosterone suppression, including hot flushes and weight increase (reported in 25% and 7%, respectively, of patients receiving treatment for one year), and injection site adverse events. Transient chills, fever or influenza like illness were reported to occur hours after dosing (in 3%, 2% and 1% of patients, respectively).The injection site adverse events reported were mainly pain and erythema, reported in 28% and 17% of patients, respectively, less frequently reported were swelling (6%), induration (4%) and nodule (3%). These events occurred primarily with the starting dose whereas during maintenance therapy the incidence of these events per 100 injections was: 3 for pain and <1 for erythema, swelling, nodule and induration. The reported events were mostly transient, of mild to moderate intensity and led to very few discontinuations (<1%). Serious injection site reactions were very rarely reported such as injection site infection, injection site abscess or injection site necrosis that could require surgical treatment/drainage.

The frequency of undesirable effects listed below is defined using the following convention:Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000).Table 1: Frequency of undesirable effects.MedDRA System Organ Class (SOC)

Very common

Common Uncommon Rare

Blood and lymphatic system disorders

Anaemia* Neutropenic fever

Immune system disorders

Hypersensitivity Anaphylactic reactions

Metabolism and nutrition disorders

Weight increase* Hyperglycemia/Diabetes mellitus, cholesterol increased, weight decreased, appetite decreased, changes in blood calcium

Psychiatric disorders

Insomnia Depression, libido decreased*

Nervous system disorders

Dizziness, headache

Mental impairment, hypoaesthesia

Eye disorders Vision blurred

Cardiac disorders Cardiac arrhythmia (incl. atrial fibrillation), palpitations, QT prolongation* (see sections SPECIAL WARNINGS AND PRECAUTIONS FOR USE and INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION)

Myocardial infarction, cardiac failure

MedDRA System Organ Class (SOC)

Very common

Common Uncommon Rare

Vascular disorders Hot flush* Hypertension, vasovagal reaction (incl. hypotension)

Respiratory, thoracic and mediastinal disorders

Dyspnoea

Gastrointestinal disorders

Diarrhoea, nausea,

Constipation, vomiting, abdominal pain, abdominal discomfort, dry mouth

Hepatobiliary disorders

Liver transaminases increased

Bilirubin increased, alkaline phosphatase increased

Skin and subcutaneous tissue disorders

Hyperhidrosis (incl. night sweats)*, rash

Urticaria, skin nodule, alopecia, pruritus, erythema

Musculoskeletal, connective tissue and bone disorders

Musculoskeletal pain and discomfort

Osteoporosis/osteopenia, arthralgia muscular weakness, muscle spasms, joint swelling/stiffness

Renal and urinary disorders

Pollakiuria, micturition urgency, dysuria, nocturia, renal impairment, incontinence

Reproductive system and breast disorders

Gynaecomastia*, testicular atrophy*, erectile dysfunction*

Testicular pain, breast pain, pelvic pain, genital irritation, ejaculation failure

General disorders and administration site conditions

Injection site adverse reactions

Chills, pyrexia, fatigue*, influenza‑like illness

Malaise, peripheral oedema

*Known physiological consequence of testosterone suppression

HypersensitivityHypersensitivity reactions, including anaphylaxis, urticaria and angioedema, have been rarely reported post‑marketing with FIRMAGON®.

Change in bone density:Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist. It can be anticipated that long periods of testosterone suppression in men will have effects on bone density.

OVERDOSEThere is no clinical experience with the effects of an acute overdose with FIRMAGON®. In the event of an overdose the patient should be monitored and appropriate supportive treatment should be given, if considered necessary.

PHARMACODYNAMIC PROPERTIESPharmacotherapeutic group: Endocrine therapy, Other hormone antagonists and related agents, ATC code: L02BX02

Mechanism of actionDegarelix is a selective GnRH receptor antagonist (blocker) that competitively and reversibly binds to the pituitary GnRH receptors, thereby rapidly reducing the release of gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and consequently testosterone (T). Prostatic carcinoma is known to be androgen sensitive and responds to treatment that removes the source of androgen. Unlike GnRH agonists, GnRH receptor blockers do not induce a luteinizing hormone (LH) surge with subsequent testosterone surge/tumour stimulation and potential symptomatic flare after the initiation of treatment.A single dose of 240 mg FIRMAGON®, followed by a monthly maintenance dose of 80 mg, rapidly causes a decrease in the concentrations of the (LH), follicle stimulating hormone (FSH) and subsequently testosterone. The plasma concentration of dihydrotestosterone (DHT) decreases in a similar manner to testosterone.FIRMAGON® is effective in achieving and maintaining testosterone suppression well below medical castration level of 0.5 ng/ml. Maintenance monthly dosing of 80 mg resulted in sustained testosterone suppression in 97% of patients for at least one year. Median testosterone levels after one year of treatment were 0.087 ng/ml (interquartile range 0.06‑0.15) N=167.

Figure 1. Plasma testosterone levels from day 0 to 364 for degarelix 240 mg/80 mg (median with interquartile ranges)

Results of the confirmatory Phase III studyThe efficacy and safety of FIRMAGON® was evaluated in an open‑label, multi‑centre, randomized, active comparator, parallel‑group study. The study investigated the efficacy and safety of FIRMAGON® one month dosing regimens; a starting dose of 240 mg (40 mg/ml) followed by monthly doses of 160 mg (40 mg/ml) or 80 mg (20 mg/ml), in comparison to leuprorelin 7.5 mg i.m. in patients with prostate cancer requiring androgen deprivation therapy. In total 620 patients were randomized to one of the three treatment groups.Of the 610 patients randomized• 31% had localized prostate cancer• 29% had locally advanced prostate cancer• 20% had metastatic prostate cancer• 7% had an unknown metastatic status• 13% had previous curative intent surgery or radiation and a rising PSA

Baseline demographics were similar between the arms. The median age was 74 years (range 47 to 98 years). The primary objective was to demonstrate that degarelix is effective with respect to achieving and maintaining testosterone suppression to below 0.5 ng/ml, during 12 months of treatment. The lowest effective maintenance dose of 80 mg degarelix was chosen.The primary objective was to demonstrate that FIRMAGON® is effective with respect to achieving and maintaining testosterone suppression to below 0.5 ng/ml, during 12 months treatment. In total 620 patients were randomized to one of the three treatment groups. In total 504 (81%) patients completed the study. In the degarelix treatment group 240/80 mg 41 (20%) patients and in the leuprorelin treatment group 32 (16%) patients discontinued the study.

Attainment of serum testosterone (T) ≤0.5 ng/mlFIRMAGON® is effective in achieving fast testosterone suppression, see Table 2.

Table 2: Percentage of patients attaining T≤0.5 ng/ml after start of treatment.

Time FIRMAGON® 240/80 mg s.c. Leuprorelin 7.5 mg i.m.Day 1 52% 0%Day 3 96% 0%Day 7 99% 1%Day 14 100% 18%Day 28 100% 100%

Avoidance of testosterone surgeNone of the FIRMAGON® treated patients experienced a testosterone surge; there was an average decrease of 94% in testosterone at day 3. Most of the leuprorelin‑treated patients experienced testosterone surge; there was an average increase of 65% in testosterone at day 3. Surge was defined as testosterone exceeding baseline by ≥ 15% within the first 2 weeks. This difference was statistically significant (p<0.001).

Figure 2 Percentage change in testosterone from baseline by treatment group until day 28 (median with interquartile ranges).

The primary end‑point in the study was testosterone suppression rates after one year of treatment with degarelix or leuprorelin. The clinical benefit for degarelix compared to leuprorelin plus anti‑androgen in the initial phase of treatment has not been demonstrated.

Testosterone reversibilityIn a study involving patients with rising PSA after localised therapy (mainly radical prostatectomy and radiation) were administered FIRMAGON® for seven months followed by a seven months

monitoring period. The median time to testosterone recovery (>0.5 ng/ml, above castrate level) after discontinuation of treatment was 112 days (counted from start of monitoring period, i.e 28 days after last injection). The median time to testosterone >1.5 ng/ml (above lower limit of normal range) was 168 days.

Long‑term effectSuccessful response in the study was defined as attainment of medical castration at day 28 and maintenance through day 364 where no single testosterone concentration was greater than 0.5 ng/ml.

Table 3: Cumulative probability of testosterone ≤0.5 ng/ml from Day 28 to Day 364.

FIRMAGON® 240/80 mgN=207

Leuprorelin 7.5 mgN=201

No. of responders 202 194Response Rate(confidence intervals)*

97.2%(93.5; 98.8%)

96.4%(92.5; 98.2%)

* Kaplan Meier estimates within group

Attainment of prostate specific antigen (PSA) reductionTumour size was not measured directly during the clinical trial programme, but there was an indirect beneficial tumour response as shown by a 95% reduction after 12 months in median PSA for FIRMAGON®.The median PSA in the study at baseline was:• for the FIRMAGON® treatment group 19.8  ng/ml (interquartile range: P25 9.4  ng/ml,

P75 46.4 ng/ml)• for the leuprorelin 7.5 mg treatment group 17.4 ng/ml (interquartile range: P25 8.4 ng/ml,

P75 56.5 ng/ml)

Figure 3: Percentage change in PSA from baseline by treatment group until day 56 (median with interquartile ranges).

This difference was statistically significant (p<0.001) for the pre‑specified analysis at day 14 and day 28.Prostate specific antigen (PSA) levels are lowered by 64% two weeks after administration of FIRMAGON®, 85% after one month, 95% after three months, and remained suppressed (approximately 97%) throughout the one year of treatment.From day 56 to day 364 there were no significant differences between FIRMAGON® and the comparator in the percentage change from baseline.

Effect on prostate volumeThree months therapy with degarelix (240/80 mg dose regimen) resulted in a 37% reduction in prostate volume as measured by trans‑rectal ultrasound scan (TRUS) in patients requiring hormonal therapy prior to radiotherapy or in patients who were candidates for medical castration. The prostate volume reduction was similar to that attained with goserelin plus anti‑androgen protection.

Effect on QT/QTc intervalsIn the randomized, active‑controlled trial comparing FIRMAGON® to leuprolide, periodic electrocardiograms were performed. Seven patients, three (<1%) in the pooled degarelix group and four (2%) patients in the leuprolide 7.5 mg group, had a QTcF ≥500 msecs. From baseline to end of study, the median change for FIRMAGON was 12.3 msec and for leuprolide was 16.7 msec. A thorough QT study showed that there was no intrinsic effect of degarelix on QT/QTc interval. The lack of intrinsic effect of degarelix on cardiac repolarization (QTcF), heart rate, AV conduction, cardiac depolarization, or T or U wave morphology was confirmed in healthy men (N=80) receiving an i.v. infusion of degarelix over 60 min, reaching a mean Cmax of 222 ng/ml approx. 3‑4‑fold the Cmax obtained during prostate cancer treatment.

Anti‑degarelix antibodiesAnti‑degarelix antibody development has been observed in 10% of patients after treatment with FIRMAGON® for one year and 29% of patients after treatment with FIRMAGON® for up to 5.5 years. There is no indication that the efficacy or safety of FIRMAGON® treatment is affected by antibody formation after up to 5.5 years of treatment.

PHARMACOKINETICS PROPERTIESThe concentration of the injected solution strongly influences the pharmacokinetic behaviour. Therefore, no other dose concentration than the recommended should be used.

AbsorptionFollowing subcutaneous administration of 240 mg degarelix at a concentration of 40 mg/ml to prostate cancer patients in the pivotal study CS21, AUC0‑28 days was 635 (602‑668) day*ng/ml, Cmax was 66.0 (61.0‑71.0) ng/ml and occurred at tmax at 40 (37‑42) hours. Mean trough values were approximately 11‑12 ng/ml after the starting dose and 11‑16 ng/ml after maintenance dosing of 80 mg at a concentration of 20 mg/ml. Cmax degarelix plasma concentration decreases in a biphasic fashion, with a mean terminal half‑life (t1/2) of 29 days for the maintenance dose. The long half‑life after subcutaneous administration is a consequence of a very slow release of degarelix from the depot formed at the injection site(s). The pharmacokinetic behavior of the medicinal product is influenced by its concentration in the solution for injection. Thus, Cmax and bioavailability tend to decrease with increasing dose concentration while the half‑life is increased. Therefore, no other dose concentrations than the recommended should be used.Following subcutaneous administration of 240 mg FIRMAGON® at a concentration of 40 mg/ml to prostate cancer patients, degarelix is eliminated in a biphasic fashion, with a median terminal half‑life (t½) of approximately 43 days for the starting dose of 240 mg (40 mg/ml) and 28 days for the maintenance dose of 80 mg (20 mg/ml). The long half‑life after subcutaneous administration is a consequence of a very slow release of degarelix from the FIRMAGON® depot formed at the injection site(s). The pharmacokinetic behavior of the drug is strongly influenced by its concentration in the injection suspension.

DistributionThe distribution volume in healthy elderly men is approximately 1 l/kg. Plasma protein binding is estimated to be approximately 90%.

BiotransformationDegarelix is subject to common peptidic degradation during the passage of the hepato‑biliary system and is mainly excreted as peptide fragments in the faeces. No significant metabolites were detected in plasma samples after subcutaneous administration. In vitro studies have shown that degarelix is not a substrate for the human CYP450 system.

EliminationIn healthy men, approximately 20‑30% of a given dose of degarelix was excreted in the urine, suggesting that approximately 70‑80% is excreted via the hepato‑biliary system in humans. The clearance in healthy elderly men is 35‑50 ml/h/kg.

Special populations:Patients with renal impairmentNo pharmacokinetic studies in renally impaired patients have been conducted. Only about 20 of a given dose of degarelix is excreted unchanged by the kidneys. A population pharmacokinetics analysis of the data from the confirmatory Phase III study has demonstrated that the clearance of degarelix in patients with mild to moderate renal impairment is reduced by 20‑30%; therefore, dose adjustment in patients with mild or moderate renal impairment is not recommended. Data on patients with severe renal impairment is scarce and caution is therefore warranted in this patient category.

Patients with hepatic impairmentDegarelix has been studied in a pharmacokinetic study in patients with mild to moderate hepatic impairment. No signs of increased exposure in the hepatically impaired were observed compared to healthy subjects. Dose adjustment is not necessary in patients with mild or moderate hepatic impairment. Patients with severe hepatic dysfunction have not been studied and caution is therefore warranted in this group.

Geriatric Use Of the total number of subjects in clinical studies of FIRMAGON®, 82% were age 65 and over, while 42% were age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

PRECLINICAL SAFETY DATAAnimal reproduction studies showed that degarelix caused infertility in male animals. This is due to the pharmacological effect; and the effect was reversible.

In female reproduction toxicity studies degarelix revealed findings expected from the pharmacological properties. It caused a dosage dependent prolongation of the time to mating and to pregnancy, a reduced number of corpora lutea, increased number of pre‑ and post‑implantation loss, an increased number of abortions, an increased number of early embryo/foetal deaths, an increased number of premature delivery and an increased duration of parturition.

The data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential.No target organ toxicity was observed from acute, subacute and chronic toxicity studies in rats and monkeys following subcutaneous administration of degarelix. Drug‑related local irritation was noted in animals when degarelix was administered subcutaneously in high doses.

LIST OF EXCIPIENTSPowder: MannitolSolvent: Water for Injection

INCOMPATIBILITIESIn the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

SHELF‑LIFEPlease see the package.After reconstitution (see section Special precautions for disposal and other handling) the product should be injected immediately.Chemical and physical in‑use stability of the reconstituted suspension has been demonstrated for 2 hours at 25ºC after solvent addition. From a microbiological point of view, once reconstituted, the product should be administered immediately.

SPECIAL PRECAUTION FOR STORAGEStore below 30°C. Do not freeze.For storage conditions of the reconstituted medicinal product, see section Shelf life.

NATURE AND CONTENTS OF CONTAINER80 mgGlass (type I) vial with bromobutyl rubber stopper and aluminium flip‑off seal containing 80 mg powder for solution for injectionPre‑filled glass (type I) syringe with elastomer plunger stopper, tip cap and line‑marking at 4 ml containing 4.2 ml solventPlunger rodVial adapterInjection needle (25G 0.5 x 25 mm)Pack sizes:1 pack containing 1 powder vial, 1 solvent pre‑filled syringe, 1 plunger rod, 1 vial adapter and 1 needle.

120 mgGlass (type I) vials with bromobutyl stopper and aluminium flip‑off seal containing 120 mg powder for solution for injectionPre‑filled glass (type I) syringes with elastomer plunger stopper, tip cap and line‑marking at 3 ml containing 3 ml solventPlunger rodsVial adaptersInjection needles (25G 0.5 x 25 mm)Pack size:1 pack containing 2 powder vials, 2 solvent pre‑filled syringes, 2 plunger rods, 2 vial adapters and 2 needles.

SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLINGThe instructions for reconstitution must be followed carefully.Administration of other concentrations is not recommended because the gel depot formation is influenced by the concentration. The reconstituted solution should be a clear liquid, free of undissolved matter.

NOTE:• THE VIALS SHOULD NOT BE SHAKEN

80 mgThe pack contains one vial of powder and one pre‑filled syringe with solvent that must be prepared for subcutaneous injection.

1. Remove the cover from the vial adapter pack. Attach the adapter to the powder vial by pressing the adapter down until the spike pushes through the rubber stopper and the adapter snaps in place.

2. Prepare the pre‑filled syringe by attaching the plunger rod.

3. Remove the cap of the pre‑filled syringe. Attach the syringe to the powder vial by screwing it on to the adapter. Transfer all solvent to the powder vial.

4. With the syringe still attached to the adapter, swirl gently until the liquid looks clear and without undissolved powder or particles. If the powder adheres to the side of the vial above the liquid surface, the vial can be tilted slightly. Avoid shaking to prevent foam formation.A ring of small air bubbles on the surface of the liquid is acceptable. The reconstitution procedure usually takes a few minutes, but may take up to 15 minutes in some cases.

5. Turn the vial upside down and draw up to the line mark on the syringe for injection.Always make sure to withdraw the precise volume and adjust for any air bubbles.

6. Detach the syringe from the vial adapter and attach the needle for deep subcutaneous injection to the syringe.

7. Perform a deep subcutaneous injection. To do so: grasp the skin of the abdomen, elevate the subcutaneous tissue and insert the needle deeply at an angle of not less than 45 degrees.Inject 4 ml of FIRMAGON® 80 mg slowly, immediately after reconstitution*.

8. No injections should be given in areas where the patient will be exposed to pressure, e.g. around the belt or waistband or close to the ribs.Do not inject directly into a vein. Gently pull back the plunger to check if blood is aspirated. If blood appears in the syringe, the medicinal product can no longer be used. Discontinue the procedure and discard the syringe and the needle (reconstitute a new dose for the patient).

120 mgThe pack contains two vials of powder and two pre‑filled syringes with solvent that must be prepared for subcutaneous injection. Hence, the procedure described below need to be repeated a second time.

1. Remove the cover from the vial adapter pack. Attach the adapters to the powder vial by pressing the adapter down until the spike pushes through the rubber stopper and the adapter snaps in place.

2. Prepare the pre‑filled syringe by attaching the plunger rod.

3. Remove the cap of the pre‑filled syringe. Attach the syringe to the powder vial by screwing it on to the adapter. Transfer all solvent to the powder vial.

4. With the syringe still attached to the adapter, swirl gently until the liquid looks clear and without undissolved powder or particles. If the powder adheres to the side of the vial above the liquid surface, the vial can be tilted slightly. Avoid shaking to prevent foam formation.A ring of small air bubbles on the surface of the liquid is acceptable. The reconstitution procedure usually takes a few minutes, but may take up to 15 minutes in some cases.

5. Turn the vial upside down and draw up to the line mark on the syringe for injection.Always make sure to withdraw the precise volume and adjust for any air bubbles.

6. Detach the syringe from the vial adapter and attach the needle for deep subcutaneous injection to the syringe.

7. Perform a deep subcutaneous injection. To do so: grasp the skin of the abdomen, elevate the subcutaneous tissue and insert the needle deeply at an angle of not less than 45 degrees.Inject 3  ml of FIRMAGON® 120  mg slowly, immediately after reconstitution.*

8. No injections should be given in areas where the patient will be exposed to pressure, e.g. around the belt or waistband or close to the ribs.Do not inject directly into a vein. Gently pull back the plunger to check if blood is aspirated. If blood appears in the syringe, the medicinal product can no longer be used. Discontinue the procedure and discard the syringe and the needle (reconstitute a new dose for the patient).

9. Repeat the reconstitution procedure for the second dose. Choose a different injection site and inject 3 ml.

* Chemical and physical in‑use stability has been demonstrated for 2 hours at 25ºC. From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in‑use storage times and conditions are the responsibility of the user.

No special requirements for disposal.

Lyophilized powder and Solvent manufacturer :

Ferring GmbHWittland 11, D‑24109 Kiel, Germany

Packager :Ferring International Center SAChemin de la Vergognausaz 50,1162 Saint‑Prex, Switzerland

05 May 2017

Leaflet FIRMAGON pref syr powd and solv for sol for inj vial

P. Black.

N/A

N/A

N/A

2009054860

02

3069

308613

2009054860