Isoniazid 於膀胱癌 case 之處方討論 報告者 : 梁心怡

Isoniazide100mg/tab 3# QD PO X 14 days Malignant neoplasm of bladder Hematuria 泌尿道感染, 未標示位置者 12/29

膀胱癌是生殖泌尿系統腫瘤中很常見的一種，其中表淺性膀 胱癌約佔 7 成左右，在治療上如果早期發現，可以經尿道使用 膀胱鏡刮除膀胱腫瘤 (TUR-BT) ，再使用抗癌藥物 /BCG 由膀 胱灌注治療，可達到相當好的治療效果。 ImmuCyst® (BCG 免疫治療劑 ) - 是由 Bacilus Calmmette-Guerin(BCG) 之 Connaught 菌株 ( 一 種牛的結核桿菌 Mycobacterium bovis 的活減毒菌株 ) 所製成 的凍 晶乾燥製劑. - 美國 FDA 於 1990 年核准 BCG 用於治療膀胱癌 。 臨床上 BCG 主要是用來： 1. 膀胱原位癌 (CIS) 的治療。 2. 預防表淺性膀胱癌 TUR( 經尿道切除術 ) 手術後的復發 3. 殘留膀胱腫瘤的治療

治療計劃 - 經膀胱投予 ImmuCyst ® 須開始於生檢或經尿道切除術 (TUR) 後 7-14days 。包括 induction therapy and maintenance therapy 。 induction therapy( 誘導療程 ) - qwk X 6 wks. 暫停 6wks, 再 qwk X 1~3wks 。 maintenance therapy( 維持療程 ) - 開始治療後 6 個月,q6mth X 1~3wks, 直到第 36 個月為止 。

BCG 免疫治療劑相關的不良反應與治療建議 症狀或症候群治療 (1) 刺激性膀胱症狀 <48 小時症狀治療 (2) 刺激性膀胱症狀 >48 小時症狀治療 延遲下一次 ImmuCyst ® 療程至症狀消除為止。 若一週內症狀能未消除，可投與 isoniazid 300mg qd 直到 完全緩解為止 (3) 伴隨 UTI( 細菌性尿路感染 ) 延遲下一次 ImmuCyst ® 療程至抗微生物療程完成後，且 尿液培養呈現陰性反應為止 (4) 其他生殖泌尿系統不良反應 : 症候 性肉芽腫性攝護腺炎，副睪丸炎，輸 尿管阻塞，或腎臟膿腫。 停用 ImmuCyst ® 投與 isoniazid 300mg qd 和 rifampin 600mg qd 3-6 months (5)fever<38.5 O C; 持續＜４８ hrs 使用 acetaminophen 做症狀治療 (6) 皮膚發癢，關節痛，或遷移性關 節炎 使用 antihistmines 或 NSAIDS 若無效，停用 ImmuCyst ® ，並投與 isoniazide 300mg qd 3months (7) 全身性的 BCG 反應不具敗血性休 克症候群 停用 ImmuCyst ® ，尋求傳染病諮詢。 投與 isoniazide300mg qd ， RIF 600mg qd and EMB 1000mg qd 6months (8) 全身性的 BCG 反應具有敗血性休 克症候群 同 (7) 考慮短時間投與高劑量 corticosteroids 治療

ISONIAZIDE THERAPEUTIC USES IN MICROMEXTHERAPEUTIC USES ISONIAZID THERAPEUTIC USES –ACETYLATOR STATUS DETERMINATIONACETYLATOR STATUS DETERMINATION –BLADDER CANCER - PREVENTION OF TOXICITYBLADDER CANCER - PREVENTION OF TOXICITY –CEREBELLAR TREMORCEREBELLAR TREMOR –HUNTINGTON'S DISEASEHUNTINGTON'S DISEASE –MULTIPLE SCLEROSISMULTIPLE SCLEROSIS –MYCOBACTERIAL INFECTIONS - NON-TUBERCULOUSMYCOBACTERIAL INFECTIONS - NON-TUBERCULOUS –TUBERCULOSIS - IN HIV-INFECTED PERSONSTUBERCULOSIS - IN HIV-INFECTED PERSONS –TUBERCULOSIS - LATENTTUBERCULOSIS - LATENT –TUBERCULOSIS - PULMONARYTUBERCULOSIS - PULMONARY

CLINICAL APPLICATIONS –THERAPEUTIC USESTHERAPEUTIC USES BLADDER CANCER - PREVENTION OF TOXICITY –1. OVERVIEW: FDA APPROVAL: Adult, no; pediatric, no EFFICACY: Adult, possibly effective DOCUMENTATION: Adult, poor –2. SUMMARY: Isoniazid maybe useful in reducing local adverse effects associated with BCG bladder instillations in patients with superficial bladder cancer.

-Isoniazid administered concomitantly with bladder instillations of bacillus Calmette-Guerin (BCG) significantly reduced local BCG-related adverse effects in adult patients with superficial bladder cancer. In this randomized, prospective, double-blind study, 160 patients received isoniazid 300 milligrams (mg) or placebo daily for 3 days after each of 6 consecutive weekly BCG bladder instillations (81 mg). All patients underwent transurethral tumor resection or bladder biopsies 1 to 3 weeks prior to initiating BCG treatment. -Local effects, including dysuria, hematuria, and increased micturation frequency, occurred less frequently in isoniazid- treated patients (35% versus 48%, p less than 0.01). This may be a result of decreased exposure to live bacilli. -Systemic side effects, such as fever and nausea, were unaffected by the addition of isoniazid. Treatment withdrawals due to adverse effects, as well as tumor recurrences over a 2- year follow-up period, were not different between groups (Al Khalifa, 2000).

ISONIAZID MECHANISM OF ACTIONMECHANISM OF ACTION IN MICROMEDEX -Isoniazid is a synthetic antimycobacterial agent which is bacteriocidal for both extracellular and intracellular organisms. The drug is thought to act by interfering with cell wall mycolic acid synthesis (AMA, 1986). Isoniazid is the hydrazide derivative of isonicotinic acid. While isoniazid is bacteriostatic for "resting bacilli", it is bactericidal for rapidly dividing organisms. In contrast to streptomycin, another antitubercular agent, isoniazid penetrates cells easily and is equally effective against intracellular bacilli as it is against those growing in culture media (Mandell & Saude, 1985). ImmuCyst®(BCG 免疫治療劑 ) 所含的為 活的減毒的分枝桿菌 故 isoniazid 可預防及治療 BCG 免疫治療劑經膀胱灌注所引起的不良反應。

Metformin 500mg/tab 1# PO TID X 7days Amoxacillin 500mg/cap 1# PO QID X 7days Bacillus Calmette-Guerin(BCG)81mg/vail 1vial IVCT ST DM Malignant neoplasm of bladder 11/24

Tranexamic acid 250mg/cap 2# PO TID X 3days Alfuzosin XL 10mg/tab 1# PO HS X 3days 11/29

Tranexamic acid 250mg/cap 2# PO TID X 3days Alfuzosin XL 10mg/tab 1# PO HS X 3days Amoxacillin 500mg/cap 1# PO TID X 3days Hematuria 12/3

Isoniazide100mg/tab 3# QD PO X 7 days Hematuria 12/23

Isoniazide100mg/tab 3# QD PO X 14 days Malignant neoplasm of bladder Hematuria 泌尿道感染, 未標示位置者 12/29

Reference 1.Micromedex 2.MIMS 3. 仿單