部份中文ImmuCyst处方资料（仅供参考） 商品名: BCG IMMUNOTHERAPEUTIC 中文名: 巴斯德 BCG 免疫治疗剂 学名: BCG vaccine 类别: INT 剂量 结构式: 每瓶含有81mg(乾重) BCG和5% Monosodium glutamate。 BCG桿菌经重新调配后可存活，每剂含6.6-19.2 X 108菌落形成单位(CFC)。 药理作用 BCG免疫治疗剂促进膀胱处其有组织细胞及白血球细胞渗透的局部发炎。局部发炎作用因膀胱表面癌损伤之明显去除或减少而引起。其真正之机转未明。 适应症 本品(BCG免疫治疗剂)适用於膀胱内使用，治疗膀胱之初级復发性原位癌(CIS)，以降低肿瘤再发之频率。其适用於治疗伴有或未伴有乳头状肿瘤之原位癌。但不适用於治疗单独发生之乳头状瘤。本品亦用作膀胱对其他原位癌(CIS)治疗疗程无法反应后之补救疗法。 治疗及预防膀胱原发或復发性原位癌或经尿道切除后之表浅性乳头瘤（ＴＡ及Ｔ１）。 用法用量 膀胱内治疗及预防膀胱原位癌(CIS)应於切片检查或经尿道切除手术后7至14天开始。一次剂量3小瓶，本品(BCG免疫治疗剂)由膀胱内投举每週一次歷时6週(诱导疗法)。各次剂量(3瓶调製好小瓶)再用50毫升减菌，无防腐剂之食盐水稀释，总量为53毫升。尿道导管在无菌状况下插入膀胱内，引导膀胱内容物，然后藉重力缓慢将50毫升本品悬浮液灌入，之后取出导管。 灌注后之第一小时内，患者应採俯卧、平躺及左右两侧躺15分鐘，然后患者可站立但再保持悬浮液60分鐘，总计达2小时，应教导其若需要以较少时间排尿。2小时终了时，为安全理由，所有患者以坐姿排尿。应教导患者保持足够之水份。达到最理想反应所需灌注之真正次数仍未知。大多数有反应之患者用6至12次灌注时达到。 不良反应 1. 大多数局部不良反应发生於第三次膀胱内灌注后，最常见者如下，排尿困难、频尿、血尿、膀胱炎、急迫、尿路感染、尿失禁及痉挛/疼痛、症状通常开始於灌注后2至4小时，持续24至72小时。 2. 每一次灌注后全身性反应一般持续1～3天，最常见者如下，身体不适、发热(>38℃)、发冷、贫血、噁心/呕吐、厌食、肌肉痛/关节痛/关节炎、腹泻、白血球过少、肾毒性及生殖器疼痛、颗粒肉牙肿性前列腺炎、副睪炎、睪丸炎以及肾肿疡已有报告已有报告挫伤性插管后或尿道感染之状况使用本品造成死亡。 3. 因使用本品所引起的刺激性小水泡副作用，可用phenazopyridinehy-drochlorid(Pyridium), probanthelia Bromide(ProBanthine)及 acetaminophen处理。 4. 全身性副作用(如身体不适，发烧及发冷)代表过敏反应，可用diphenhydraminhydrochloride治疗、用膀胱内本品偶而会发生因BCG菌种分佈所引起全身性感染、此种状况之处理於预防措施处提供。 禁忌 1. 正使用免疫抑制治疗的患者或免疫系统受损之患者不应接受ImmucCysTM(BCG免疫治疗剂)因有无法抵抗分枝桿菌而可能会造成全身性之败血症。 2. 骨髓抑制剂及/或免疫抑制剂及/或放射物之药物互相组合可能会损害本品之反应，而增加骨髓炎或散佈性BCG感染之危险性。 3. 除非发烧之原因已被测定且评估过，否则本品不应投药给发烧之患者、若发生之原因为感染，则应停用本品，直至烧退。 4. 尿路感染之患者不应接受本品治疗，因其会有造成散佈性BCG感染之危险性或增加膀胱刺激之危险性。 注意事项 1. 本品因含活的减毒分枝桿菌，以传染物处理。 2. 所有用以灌注本品进入膀胱的装置及材料(例如：针筒、导管)在使用后应立即置入胶袋内，袋上标有\"感染性废弃物\"并依据生物危险废弃物丢弃。 3. 使用本品(BCG免疫治疗剂)治疗膀胱原位癌时必须小心，不要引污染入尿道造成不当地伤害尿路粘膜。 4. 建议经尿道切除后一週内不可投用膀胱内本品，因为外伤性插管后使用本品已有死亡之报告。 5. 若医师相信膀胱插管已造成外伤(例如：引起出血或可能之歧道)，则不应使用本品，治疗至少须延后一过。接下去应用完所有本品剂量，即使曾暂时性停止投药亦是。 6. 若於治疗期间患者有发烧或严重的身体不适，应投用isoniazid，每天300mg，直至症状缓解止。若症状持续，则应停止BCG免疫法。以后任何重新灌注BCG前应开始Isoniazid预防性治疗。 7. 若有怀疑全身性BCG感染(即患者若发热超过39℃或发热高过 38℃时持续2天或严重身体不适)应开始用isoniazid每天300 mg Rifampicin 600mg/天，及ethambutol 120mg/天作快速作用抗结核病疗法。停止BCG疗法，且应请询传染病专家。应加 cycloserine 250～500mg 以对致命性感染作紧急治疗。应该知道假定性BCG全身感染仅少见地由阳性培养确定。 8. 怀孕时使用：尚未使用本品进行动物生殖研究。亦未知本品投用到怀孕妇女是否造成胎儿伤害，或是否会影响生育能力。只有清楚明确地需要本品方能给予怀孕妇女使用。 9. 哺乳母亲：全身性BCG感染之母亲会传染其餵乳之婴儿。未知本品是否排出在人类乳汁中。因此当投用本品至哺乳母亲时应小心。儿童使用：对儿童CIS之安全性及效力尚未确立。 孕妇用药分级 C 级： 在对照的动物研究试验中显示该药学物对胚胎有不良反应（致畸胎性或杀胚胎性或其他），但未进行人体怀孕妇女研究；或者尚无对照的人体怀孕妇女或动物研究试验。只有在可能的利益大於潜在的危险，才可使用此药物。 药品保存方式 药品应置於摄氏 2 ~ 8度冰箱内(勿冷冻)；如发生变质或过期，不可再使用。 ImmuCyst 81mg 1. Name of the medicinal product ImmuCyst® 81 mg powder for intravesical suspension 2. Qualitative and quantitative composition ImmuCyst® 81 mg is freeze-dried preparation made from the Connaught substrain of Bacillus Calmette-Guérin (BCG), which is an attenuated strain of Mycobacterium bovis. The bacilli are lyophilised (freeze-dried) and are viable upon reconstitution. The product contains no preservative. Lyophilisate BCG Immunotherapy (Connaught substrain of Bacillus Calmette-Guérin) Content per Vial 81 mg (dry weight) 1.8 to 15.9 x 108 Colony Form Units For a full list of excipients, see section 6.1. 3. Pharmaceutical form Powder for intravesical suspension. ImmuCyst® 81 mg is a freeze-dried white powder which is free from preservatives. 4. Clinical particulars 4.1 Therapeutic indications ImmuCyst® 81 mg is indicated for intravesical use in the treatment of primary or recurrent carcinoma in situ (CIS) of the urinary bladder, for the prophylaxis of recurrence of CIS of the urinary bladder and for the prophylaxis following transurethral resection (TUR) of primary or recurrent stage Ta and/or T1 papillary tumours, or any combination thereof, regardless of antecedent intravesical treatment. 4.2 Posology and method of administration Posology Adults One dose of ImmuCyst® 81 mg consists of the intravesical instillation of 81 mg BCG. Intravesical treatment of the urinary bladder should begin a minimum of 14 days after biopsy or TUR (see section 4.3) and consists of induction and maintenance therapy. • The induction therapy schedule consists of one intravesical instillation of ImmuCyst® 81mg each week for 6 weeks for a total of 6 doses. • After a 6 week pause, one intravesical dose should be given each week for 1 to 3 weeks. Clinical studies have demonstrated that 3 weekly instillations significantly increase the complete response rate from 73% to 87% at 6 months, compared with no additional treatment given at 3 months. Three weekly instillations should definitely be given to patients who still have evidence of bladder cancer. • Based on clinical studies performed with ImmuCyst® 81 mg, maintenance therapy following induction is highly recommended. This consists of one dose given each week for 1 to 3 weeks at 6, 12, 18, 24, 30 and 36 months following the initiation of induction treatment. Paediatric population The safety and efficacy in children have not been established. Method of Administration This dose is prepared by reconstituting and diluting the freeze-dried BCG with sterile, preservative-free saline, to a total of 50 ml instillation volume (see instructions for use and handling). A urethral catheter is inserted into the bladder under aseptic conditions. It is important to note that a sufficient quantity of lubricant is used to reduce the chance of traumatising the urinary mucosa and therefore the risk of severe complications including BCG infection and also to reduce the discomfort of the patient. From the limited evidence, bacteriostatic urethral lubricants have been shown to have an association with a reduction in the viability of BCG (see section 4.5). As a precaution, to minimise the amount of lubricant in the bladder, it is recommended that catheterisation should be performed when the bladder is full. The bladder is drained, rinsing out with the urine any lubricant which may have reached the bladder. The 50 ml suspension of ImmuCyst® 81 mg is instilled slowly by gravity, following which the catheter is withdrawn. The patient retains the suspension for as long as possible for up to two hours. During the first 15 minutes following instillation, the patient should lie prone. Thereafter, the patient is allowed to be up. At the end of 2 hours, all patients should void in a seated position for environmental safety reasons (see sections 4.4 and 6.6). Unless medically contraindicated patients should be instructed to increase fluid intake in order to flush the bladder in the hours following BCG treatment. 4.3 Contraindications ImmuCyst® 81 mg is contraindicated for patients: • with known systemic hypersensitivity reaction to any component (see sections 4.4 and 6.1) of ImmuCyst® 81 mg or after previous administrations of the medicinal product or a medicinal product containing the same substance, • who have had a biopsy, TUR or traumatic bladder catheterisation (associated with haematuria) in the previous 14 days, • who are immunosuppressed as a result of malignancies or receiving immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs (see section 4.5), or who are otherwise immunocompromised (including HIV-infected individuals), • with active tuberculosis, because of the danger of exacerbation or of concomitant systemic BCG infection; active tuberculosis should be ruled out before starting treatment with ImmuCyst® 81 mg, • with current or previous evidence of a systemic BCG infection (see section 4.4), • with concurrent febrile illness, urinary tract infection, or macroscopic haematuria; treatment with ImmuCyst® 81 mg should be postponed until their resolution (see sections 4.4 and 6.1). 4.4 Special warnings and precautions for use For intravesical instillation only. Do not inject subcutaneously, intradermally or intravenously. Special warnings Systemic BCG Reaction A systemic BCG reaction, which may be fatal, is a systemic granulomatous illness, which may occur (although rarely) subsequent to exposure to BCG. Because it is usually difficult to isolate BCG organisms from affected organs, it is often unclear to what extent such a reaction is caused by an infectious process versus an inflammatory hypersensitivity reaction, hence the term “systemic BCG reaction”. Based on past clinical experience with intravesical BCG, “systemic BCG reaction” may be defined as the presence of any of the following signs, if no other aetiologies for such signs are detectable: fever >39.5°C for 12 hours; fever >38.5°C for 48 hours; pneumonitis; hepatitis; other organ dysfunction outside of the genitourinary tract with granulomatous inflammation on biopsy; or the classical signs of sepsis, including circulatory collapse, acute respiratory distress and disseminated intravesicular coagulation (see section 4.8). Although rare, a systemic BCG reaction is much more likely to occur if ImmuCyst® 81 mg is administered within one week of biopsy, TUR or traumatic bladder catheterisation (associated with haematuria). Ectopic BCG infection The risk of these ectopic BCG infections has not been determined but is considered to be very small. The benefits of BCG therapy must be carefully weighed against the possibility of ectopic BCG infection in patients with arterial aneurysms or prosthetic devices of any kind. Some male genitourinary tract infections (orchitis/epididymitis) have required orchiectomy. Immunosuppressive treatments For patients with a condition that may in future require mandatory immunosuppression (e.g. awaiting organ transplant, myasthenia gravis) the decision to treat with ImmuCyst® 81 mg should be considered carefully. Other warnings The stopper of the vial for this product contains natural rubber latex, which may cause allergic reactions. For patients with small bladder capacity, increased risk of bladder contracture should be considered in decisions to treat with ImmuCyst® 81 mg. If a bacterial urinary tract infection (UTI) occurs during the course of ImmuCyst® 81 mg treatment, ImmuCyst® 81 mg instillation should be withheld until complete resolution of the bacterial UTI for two reasons: (1) the combination of a UTI and BCG- induced cystitis may lead to more severe adverse effects on the genitourinary tract, and (2) BCG bacilli are sensitive to certain antibiotics; antimicrobial administration may therefore diminish the efficacy of ImmuCyst® 81 mg. ImmuCyst® 81 mg is not recommended for prophylactic treatment following TUR of stage TaG1 papillary tumours unless they are judged to be at high risk of tumour recurrence. Intravesicular treatment with ImmuCyst® 81 mg may induce sensitivity to tuberculin purified protein derivative (PPD) which could complicate future interpretations of skin test reactions to tuberculin in the diagnosis of suspected mycobacterial infections. Determination of a patient's reactivity to tuberculin prior to administration of ImmuCyst® 81 mg may therefore be desirable. Special precautions for use Contains viable attenuated mycobacteria. Handle as infectious. ImmuCyst® 81 mg should be prepared and handled using aseptic technique (see sections 4.2 and 6.6). BCG infections have been reported in health-care workers preparing BCG for administration. ImmuCyst® 81 mg should not be handled by persons with immune deficiency. Given the specialised nature of BCG intravesical treatment, ImmuCyst® 81 mg should be administered under the supervision of a qualified physician, such as a urologist, experienced in the use of anti-cancer agents. Nosocomial infections have been reported in immunosuppressed patients. ImmuCyst® 81 mg should not be handled in areas where parenteral drugs are prepared. Serious and Severe Adverse Event Related Precautions Care must be taken during administration of intravesicular ImmuCyst® 81 mg not to introduce contaminants into the urinary tract nor to traumatise unduly the urinary mucosa. If the physician believes that the bladder catheterisation has been traumatic (e.g. associated with bleeding), then ImmuCyst® 81 mg should not be administered and there must be a treatment delay of at least 14 days. Subsequent treatment should be resumed as if no interruption in the schedule had occurred. Patients should be monitored for the presence of symptoms and signs of toxicity after each intravesical treatment. If a patient develops persistent fever or experiences an acute febrile illness consistent with BCG infection, BCG instillations should be permanently discontinued, the patient immediately evaluated and treated for BCG infection and an infectious diseases consultation sought (see section 4.8). As standard therapy for BCG infection, treatment with two or more antimycobacterial agents must be initiated promptly while diagnostic evaluation, including cultures, is conducted. Use of single antibiotic therapy is not recommended. Negative cultures do not necessarily rule out infection. Advice for patients Fever, chills, malaise, flu-like symptoms, increased fatigue or an increase in urinary symptoms (such as burning or pain on urination) can occur. However, patients should be advised to notify their physicians if any of these symptoms last more than 48 hours or increase in severity. Patients should also notify their physicians if they experience any of the following: an increase in urinary symptoms (such as urgency, frequency of urination, blood in urine), joint pain, eye complaints (such as pain, irritation or redness), cough, skin rash, jaundice, nausea or vomiting. Because ImmuCyst® 81 mg contains live mycobacteria, excreted urine may also contain live bacteria. Patients should be advised on appropriate infection control procedures to protect family and close contacts from infection. ImmuCyst® 81 mg is retained in the bladder for as long as possible up to 2 hours and then voided. To avoid transmission of BCG to others, for 6 hours after treatment, patients should void while seated to avoid splashing urine. Urine voided during this time should be disinfected with an equal volume of household bleach for 15 minutes before flushing or disposal. Unless medically contraindicated, patients should be instructed to increase fluid intake to “flush” the bladder for several hours following treatment with ImmuCyst® 81 mg. Patients may experience burning with the first void after treatment. 4.5 Interaction with other medicinal products and other forms of interaction Immunosuppressive Treatments Treatment combinations using immunosuppressants and/or radiation interfere with the immune response to ImmuCyst® 81 mg and increase the risk of disseminated BCG infection. Antibacterial Drugs Antimicrobial therapy for other infections may interfere with the effectiveness of ImmuCyst® 81 mg. Therefore, patients undergoing antimicrobial therapy should be evaluated to assess whether the therapy might diminish the efficacy of ImmuCyst® 81 mg. Limited in-vitro testing of bacteriostatic lubricants and BCG has shown a reduction in the number of BCG CFU. However, it has been shown in patients that when a bacteriostatic lubricant was used for catheterisation before instillation, the BCG CFU count remained above the required minimum microbial count and there was no significant reduction in the clinical efficacy of BCG therapy. Antituberculosis Drugs Antituberculosis drugs should not be used prophylactically to prevent the local, irritative side effects of ImmuCyst® 81 mg. There are no data to suggest that the acute, local urinary tract symptoms common with intravesical BCG are due to mycobacterial infection. ImmuCyst® 81 mg is not sensitive to pyrazinamide. 4.6 Fertility, pregnancy and lactation There are no data on the use of ImmuCyst® 81 mg in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). ImmuCyst® 81 mg should not be used during pregnancy unless the clinical condition of the woman requires treatment with ImmuCyst® 81 mg. Women of childbearing potential must use effective contraception during treatment. It is unknown whether ImmuCyst® 81 mg is excreted in human milk. A risk to the newborns/infants cannot be excluded, in particular if the nursing mother has a systemic BCG infection. Breast-feeding should be discontinued during treatment with ImmuCyst® 81 mg. 4.7 Effects on ability to drive and use machines No studies on the effect on the ability to drive and use machines have been performed. 4.8 Undesirable effects a. Summary of the safety profile Adverse event information is derived from clinical trials and worldwide post-marketing experience. Administration of ImmuCyst® 81 mg causes an inflammatory response in the bladder and can provoke signs and symptoms of cystitis (see Table 1). Such reactions may to some degree be taken as evidence that BCG is evoking the desired response, but patients should be carefully monitored for serious adverse events. Symptoms of bladder irritability are reported in approximately 50% of patients receiving ImmuCyst® 81 mg and typically begin a few hours after instillation and last 6 - 48 hours. The symptoms are usually seen following the third instillation and tend to increase in severity after each administration. The mechanism of action of the irritative side effects has not been studied, but is most consistent with an immunological mechanism. There is no evidence that dose reduction or antituberculous drug therapy can prevent or lessen the irritative symptoms of ImmuCyst® 81 mg. Undesirable effects frequencies are presented using the following convention: • Very common: (≥1/10) • Common:(≥1/100 and <1/10) • Uncommon:(≥1/1.000 and <1/100) • Rare: (≥1/10,000 and < 1/1,000) • Very rare: (<1/10,000), including isolated cases • Not known: cannot be estimated from the available data. b. Tabulated list of adverse events The clinical safety information on ImmuCyst® 81 mg is based on a dataset of 699 patients treated with ImmuCyst® 81 mg in 2 clinical trials. Table 1 below presents the frequencies of adverse events of any severity reported during the induction and maintenance courses of treatment, respectively, in study SWOG 8507 in 587 patients. Footnotes identify the adverse events reported as severe (grade >3) at uncommon and common frequency ranking respectively. Table 1: SWOG Study 8507 – Adverse Reactions Induction Maintenance Infection and Infestation Urinary Tract Infection Common Common* Systemic Infection Uncommon† Uncommon* Pulmonary Infection Uncommon† NR Infection Uncommon NR Cystitis Uncommon Common* Blood and Lymphatic System Disorders Anaemia Uncommon NR Leukopenia Uncommon NR Coagulopathy/Thrombocytopenia Uncommon† NR Metabolism and Nutrition Disorders Anorexia Common* Common* Nervous System Disorders Headache Uncommon Uncommon Dizziness Uncommon NR Cardiac Disorders Cardiac (Unclassified) Uncommon Common Gastrointestinal Disorders Nausea/Vomiting Common* Common* Diarrhoea Uncommon Common* Abdominal Pain Uncommon NR Constipation NR Uncommon Mucositis/Ulcers/Stomatitis Uncommon NR Hepatobiliary Disorders Liver Involvement Uncommon† Common Granulomatous Hepatitis Uncommon* NR Skin and Subcutaneous Tissues Disorders Skin Rash Uncommon* Common Hypersensitivity Reaction Skin NR Uncommon* Skin Abscess NR Uncommon Musculoskeletal, Connective Tissue and Bone Disorders Arthalgia/Myalgia/Arthritis Uncommon Common* Renal and Urinary Disorders Dysuria Very Common‡ Very Common‡ Hematuria Very Common§ Very Common‡ Urinary Frequency Very Common‡ Very Common‡ Urinary Urgency Common* Very Common‡ Bladder Cramps/Pain Common* Common‡ Urinary Incontinence Uncommon* Common* Renal Toxicity Uncommon Uncommon Contracted Bladder Uncommon* Common‡ Ureteral Obstruction Uncommon* NR Tissue in Urine NR Uncommon Reproductive System and Breast Disorders Genital Pain Uncommon NR General Disorders and Administrative Site Conditions Fever Very Common* Very Common‡ Malaise Very Common* Very Common‡ Chills Very Common* Very Common‡ Fatigue Common* Uncommon These events have been reported with a severity grade =3 with an Uncommon frequency rating. These events have been reported with a severity grade ≥3 with an Uncommon frequency rating. These events have been reported with a severity grade =3 with a Common frequency rating. These events have been reported with a severity grade ≥3 with a Common frequency rating. The same adverse events as shown in Table 1 were also reported during the trial SWOG 8216 in 127 patients, as was the following: Musculoskeletal, Connective Tissue and Bone Disorders: Flank pain - Uncommon The following additional adverse events have been spontaneously reported during the post-marketing use of ImmuCyst® 81 mg worldwide. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. Their frequency is considered not known. Infections and Infestations BCG Infection: BCG is capable of dissemination when administered by the intravesical route. Serious infections, including sepsis with associated mortality, have been reported. BCG infections have also been reported in eye, lung, liver, bone, bone marrow, kidney, regional lymph nodes, peritoneum, genitourinary tract (orchitis/epididymitis) and prostate (e.g. Granulomatous prostatitis). BCG infection of aneurysms and prosthetic devices (including arterial grafts, cardiac devices and artificial joints) has also been reported. Joint symptoms (arthritis, arthralgia), ocular symptoms (including conjunctivitis uveitis, iritis, keratitis, granulomatous choreoretinitis), urinary symptoms (including urethritis), skin rash, alone or in combination (Reiter's syndrome) have been reported following administration of ImmuCyst® 81 mg. For the reports of Reiter's syndrome, the risk seems to be more elevated among patients who are positive for HLA-B27. Renal abscess Respiratory, Thoracic and Mediastinal Disorders Pneumonia, interstitial lung disease Skin and Subcutaneous Tissue Disorders Erythema nodosum Renal and Urinary Disorders Renal failure, pyelonephritis, nephritis (including tubulointerstitial nephritis, interstitial nephritis and glomerulonephritis) Urinary retention (including bladder tamponade and feeling of residual urine) General Disorders and Administration Site Conditions Flu-like symptoms Investigations (Laboratory Tests) Abnormal/increased blood creatinine or blood urea nitrogen (BUN) If a systemic BCG infection has occurred, a report should be submitted to both the manufacturer and the appropriate health authorities. The report should include details of the treatment history with ImmuCyst® 81 mg, the symptoms and signs of the BCG infection, the treatment administered for the reaction, and the response to this treatment. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Tel: Freephone 0808 100 3352. Website: www.mhra.gov.uk/yellowcard 4.9 Overdose In case of overdose, patients should be monitored closely (see sections 4.4 and 4.8). 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antineoplastic and Immunomodulating Agents ATC Code: L03AX03 When administered intravesically as a cancer therapy, BCG promotes a local acute inflammatory and sub-acute granulomatous reaction with macrophage and leukocyte infiltration in the urothelium and lamina propria of the urinary bladder. 5.2 Pharmacokinetic properties Because ImmuCyst® 81 mg contains live mycobacteria, excreted urine may also contain live bacteria (see sections 4.4 and 6.6). 5.3 Preclinical safety data ImmuCyst® 81 mg administered intravesically induced no serious systemic toxicity in studies in guinea pigs and monkeys. Studies in animals suggest that there is a possibility of a potential for allergenicity to the product. No animal reproduction studies have been performed. Studies on mutagenicity and carcinogenicity have also not been performed. 6. Pharmaceutical particulars 6.1 List of excipients Monosodium glutamate 6.2 Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. 6.3 Shelf life 2 years Reconstituted Product The product should be used immediately after reconstitution. In the event of a delay between reconstitution and administration, the reconstituted and diluted suspension may be stored, protected from light, for up to 2 hours at a temperature between 2°C and 25°C. 6.4 Special precautions for storage Store in a refrigerator (2°C - 8°C). For storage conditions of the reconstituted product, see section 6.3. At no time should the freeze-dried or reconstituted ImmuCyst® 81 mg be exposed to sunlight, direct or indirect. Exposure to artificial light should be kept to a minimum. 6.5 Nature and contents of container 5 ml type 1 amber glass vial sealed with a grey butyl silicone stopper and held closed with an aluminium seal with a blue flip-off plastic top. Pack of 1 6.6 Special precautions for disposal and other handling Reconstitution of Freeze-Dried Product DO NOT REMOVE THE RUBBER STOPPERS FROM THE VIALS. HANDLE AS INFECTIOUS MATERIAL. The preparation of the ImmuCyst® 81 mg should be done using aseptic technique. A separate area for the preparation of the ImmuCyst® 81 mg suspension is recommended in order to avoid cross contamination (e.g. in a biocontainment cabinet). The person responsible for mixing the agent should wear gloves, eye protection, a mask and gown to avoid inhalation of BCG organisms and inadvertent exposure of broken skin to BCG organisms. When handling and reconstituting ImmuCyst® 81 mg, care should be taken so as to avoid needle stick injuries. ImmuCyst® 81 mg should not be handled by persons with an immunologic deficiency (see sections 4.3 and 4.4). ImmuCyst® 81 mg is to be reconstituted only with sterile preservative-free normal saline to ensure proper dispersion of the organisms. For the reconstitution and further dilution of one dose of ImmuCyst® 81 mg, 50ml of sterile preservative-free normal saline are required. Three options for intravesicular administration are possible: Option 1: • Using a 5 ml sterile syringe and needle, draw up 3ml of sterile preservative-free saline solution. • Prepare the surface of the ImmuCyst® 81 mg vial using a suitable antiseptic. • Using the same syringe and needle, pierce the rubber stopper in the vial of freeze-dried material with the needle. • Holding the vial of freeze-dried material upright, pull the plunger of the syringe back to the 5 ml marking on the barrel. This will create a mild vacuum in the vial. • Release the plunger and allow the vacuum to pull the saline from the syringe into the vial of freeze-dried material. • After all the saline has passed into the freeze-dried material, remove the needle and syringe. • Shake the vial gently until a fine, even suspension results. Avoid foaming since this will prevent withdrawal of the proper dose. Any reconstituted product, which exhibits flocculation or clumping that cannot be dispersed with gentle shaking should not be used. • Withdraw the entire contents of the reconstituted material from the vial into the same 5ml syringe. Return the vial to an upright position before removing the syringe from the vial. Further dilute the reconstituted material from the vial (1 dose) with sterile preservative-free normal saline to a final volume of 50 ml for intravesical instillation. The reconstituted product is then transferred to a bladder syringe. Option 2: Following instructions as above except the entire contents from the reconstituted vial is added to a saline bladder irrigation bag instead of a bladder syringe. Option 3: Use a 50ml (closed system) saline bladder irrigation bag to reconstitute ImmuCyst® 81 mg and instill the solution as per the manufacturer's instructions. Instructions for Disposal Unused product, packaging, and all equipment and materials used for instillation of the product (e.g. syringes, catheters) should be placed immediately in a container for biohazardous materials and disposed of according to local requirements applicable to biohazardous materials. Urine voided during the 6-hour period following ImmuCyst® 81 mg instillation should be disinfected with an equal volume of 5% hypochlorite solution (undiluted household bleach) and allowed to stand for 15 minutes before flushing. 7. Marketing authorisation holder Alliance Pharmaceuticals Limited Avonbridge House Bath Road Chippenham Wiltshire SN15 2BB UK 8. Marketing authorisation number(s) PL 16853/0120 9. Date of first authorisation/renewal of the authorisation 19 September 2001 10. Date of revision of the text 17/11/2014 イムシスト膀注用81mg 干燥卡介苗（生物反应调节剂） 产品名称（制造和销售公司） •イムノブラダー（日本BCG） •イムシスト（日本化薬） 组成 Imushisuto膀胱内为81毫克 主料： 有效成分：小瓶的一部分 活卡介苗（BCG）·诺株（干细胞重量）：81毫克 主料： 添加剂：小瓶的一部分 L-谷氨酸钠水合物：166mg 解决方案 成分： 添加剂：一小瓶的一部分（3mL）中 氯化钠 pH调节剂2分量 聚山梨酯80：为0.75mg BCG已被用于世界各地的结核病防治与减毒牛分枝杆菌制成的疫苗。虽然疫苗本身是抗癌效果并不，刺激是导致在膀胱炎的免疫系统，免疫系统已产生针对膀胱癌的抗癌效果。 膀胱注射治疗，一直被视为浅表性膀胱癌的初始治疗的首选。在高复发风险的患者常用的，80％到90％德感细胞已经被说成是完全消失。 巨蟹座指示 浅表（一直保持粘膜内）膀胱癌 主要副作用 通过刺激膀胱，大多数人，尿频和排尿疼痛，排尿困难，这将是血尿Nadogami。此外，间质性肺炎和过敏反应症状，萎缩性膀胱，还存在一种可能性，即，可能会发生莱特尔氏综合征，如肾衰竭。 使用注意事项 谁在人或结核病史结核菌素反应请求人就出来了强烈的还有上述副作用延长。 包装 1小瓶（附溶液） 完整处方资料附件：http://www.info.pmda.go.jp/go/pack/6391701X1030_3_02/