部份中文两性霉素B处方资料（仅供参考）
药品英文名
Amphotericin B
药品别名
二性霉素、二性霉素B、两性霉素乙、庐山霉素、异性霉素、芦山霉素、节丝霉素、节丝霉素B、Ampho-Moronal、AmphotericinumB、Anfotericina B、Fungilin、Fungizone
药物剂型
1.注射剂(粉)：5mg(500U)，25mg(25000U)，50mg(5万U)；
2.溶液：3%；
3.霜剂：3%；
4.软膏：3%。
药理作用
本药从链霉菌(Streptomycesnodosus)的培养液中提炼制得，是一种多烯类抗真菌抗生素。本药可与敏感真菌细胞膜上的固醇结合，损伤膜的通透性，导致细胞内重要物质如钾离子、核苷酸和氨基酸等外漏，从而破坏了细胞的正常代谢而抑制其生长。
通常临床治疗所达到的药物浓度对真菌为抑菌作用，最低抑菌浓度(MIC)为0.02～1mg/L。如药物浓度达到人体可耐受范围的高限时则对真菌起杀菌作用。
两性霉素B几乎对所有真菌均有抗菌活性，主要对念珠菌、隐球菌、组织胞浆菌、酵母菌、皮炎芽生菌、球孢子菌属等有效。部分曲霉菌对本药耐药，皮肤癣菌则大多数呈现耐药。
药动学
口服本药后自胃肠道吸收少而不稳定。成人每天口服1.6～5g，连续2天后血药浓度也仅有微量，约为0.04～0.5μg/ml，脑脊液中不能测到。
本药分布容积为4L/kg，在体液(除血液外)中浓度甚低，腹腔积液、胸腔积液和滑膜液中药物浓度通常低于同期血药浓度的一半，支气管分泌物中药物浓度亦低。
脑脊液浓度约为血浓度的2%～4%。蛋白结合率为91%～95%。氚标记本药应用于灵长类动物实验，结果显示药物组织浓度最高者为肾，其余依次递减为肝、脾、肾上腺、肺、甲状腺、心、骨骼肌、胰、腺、脑、骨。脑脊液中浓度约为血药浓度的2%～4%。蛋白结合率为91%～95%。开始每天静脉滴注1～5mg，以后逐渐增至每天0.65mg/kg时的血药峰浓度约为2～4μg/ml。
本药半衰期约为24h。
在体内经肾缓慢排出，每天约有给药量的2%～5%以药物的活性形式排出，7天内自尿中约排出给药量的40%，停药后药物自尿中排泄至少持续7周。在碱性尿中药物排泄增多。本药不易为透析所清除。
小儿常用量均参见成人，即按体重计算静脉滴注及鞘内用药量。局部用药有气溶吸入，成人每次5～10mg，以蒸馏水溶解成0.2%～0.3%溶液应用；如为超声雾化吸入，则本品浓度应为0.01%～0.02%，每天吸入2～3次，每次5～10ml。眼部或皮肤局部采用0.2%～0.3%溶液，膀胱冲洗用本品每天15～50mg，配制成0.01%～0.02%溶液应用。
适应证
1.用于治疗隐球菌病、皮炎芽生菌(北美芽生菌病)、播散性念珠菌病、球孢子菌病、组织胞浆菌病等。
2.用于治疗由毛霉菌、根霉属、犁头霉菌属、内胞霉属和蛙粪霉属等所致的毛霉病。
3.用于治疗由申克孢子丝菌引起的孢子丝菌病。
4.用于治疗由烟曲菌所致的曲霉病。
5.外用制剂适用于着色真菌病、烧伤后皮肤真菌感染、呼吸道念珠菌、曲菌或隐球菌感染、真菌性角膜溃疡。
禁忌证
对本品过敏者和孕妇禁用。严重肝病患者。
注意事项
1.慎用：肾功能不全者。
2.用药前后及用药时应当检查或监测：
(1)肾功能，定期检查尿常规、血尿素氮及血肌酐，疗程开始剂量递增时隔日测定上述各项，疗程中尿常规、血尿素氮及血肌酐至少每周2次，如测定结果血尿素氮或血肌酐值的升高具临床意义时，则需减量或停药，直至肾功能改善；
(2)周围血象和血清镁测定，治疗过程中每周测定1次；
(3)肝功能检查，如发现肝功能损害(血胆红素、碱性磷酸酶、血氨基转移酶升高等)时应停药；
(4)血钾测定，治疗过程中每周至少测定2次。
3.两性霉素B毒性大，不良反应多见，但它又常是某些严重全身真菌感染的惟一有效的治疗药物，因此必须从其拯救生命的效益和可能发生的不良反应的危险性两方面权衡考虑是否用药。
4.使用期间应用组胺拮抗剂可减轻某些反应，皮质激素也有减轻反应作用，但只限在反应较严重时，勿作为常规使用。
5.在酸性较强的药液中易降解，所用葡萄糖注射的pH值不应低于4.2。
6.静脉滴注如漏出血管外，可引起局部炎症，可用5%葡萄糖注射剂抽吸冲洗，也可加少量肝素钠注射剂于冲洗液中。
不良反应
1.在静脉给药过程中或之后发生寒战、高热、严重头痛、恶心和呕吐，有时可出现血压下降、眩晕等。
2.几乎所有患者均可出现不同程度的肾功能损害，尿中可出现红细胞、白细胞、蛋白和管型，血尿素氮及肌酐升高，肌酐清除率降低，也可引起肾小管性酸中毒。
3.使用本药后大量钾离子排出可致低钾血症。
4.血液系统毒性，可发生正常红细胞性贫血，血小板减少也偶可发生。
5.肝毒性较为少见，但由本药所致的肝细胞坏死、急性肝功能衰竭亦有发生。
6.心血管系统反应，静脉滴注过快时可引起心室颤动或心脏骤停。本药所致的电解质紊乱亦可导致心律失常的发生。两性霉素B刺激性大。注射部位可发生血栓性静脉炎。
7.神经系统毒性，视力模糊或复视、癫痫样发作，偶有多发性神经病变。本药鞘内注射后可能引起严重头痛、发热、呕吐、颈项强直、下肢疼痛、尿潴留等，严重者出现下肢截瘫。
8.偶有过敏性休克、皮疹等发生。
9.外用可有局部刺激。
10.鞘内注射可引起背部及下肢疼痛。
11.使用期间，应用抗组胺药、糖皮质激素可减轻药物反应，但糖皮质激素只限在反应较严重时用。
用法用量
1.成人：
(1)静脉滴注：开始静脉滴注时可先试从1～5mg或按体重每次0.02～0.1mg/kg给药，以后根据患者耐受情况每天或隔日增加5mg，当增加至每次0.6～0.7mg/kg时即可暂停增加剂量。最高单次剂量按体重不超过1mg/kg，每天或隔1～2天给药1次，总累积量1.5～3.0g，疗程1～3个月，也可长至6个月，需视患者病情及疾病种类而定。对敏感真菌所致感染宜采用较小剂量，即1次20～30mg，疗程仍宜较长。
(2)鞘内注射：首次为0.05～0.1mg，以后逐渐增至每次0.5mg，最大量每次不超过1mg，每周给药2～3次，总量15mg左右。鞘内给药时宜与小剂量地塞米松或琥珀酸氢化可的松同时给予，并需用脑脊液反复稀释药液，边稀释边注入以减少反应。
(3)局部用药：
①着色真菌病：以1～3mg/ml溶液加适量普鲁卡因，病灶内局部注射，每周1～2次；多病灶者可交替注射。皮肤灼烧后感染真菌，以0.1%溶液外涂；
②呼吸道真菌感染：以5～10mg，配成0.2～0.3mg/ml溶液，每天分2次喷雾，疗程1个月；
③真菌性角膜溃疡：用1%眼膏或0.1%溶液外涂，每天2次。
2.儿童：
(1)静脉滴注：每次0.5～1mg。静脉滴注时，均先以灭菌注射用水10ml配制本药50mg，或5ml配制25mg，然后用5%葡萄糖注射剂稀释(不可用氯化钠注射剂，因可产生沉淀)，避光缓慢静脉滴注，每次滴注时间需6h以上，稀释用葡萄糖注射剂的pH应在5以上；
(2)鞘内注射:每次0.5～1mg。鞘内注射时可取5mg/ml浓度的药液1ml，加5%葡萄糖注射剂19ml稀释，使最终浓度成250μg/ml。注射时取所需药液量以脑脊液5～30ml反复稀释，并缓慢注入。鞘内注射剂药物浓度不可高于250μg/ml，pH应在4.2以上。
3.肾功能不全时剂量：肾功能不全的患者建议剂量如下：肾小球滤过率每分钟大于10ml，给药间隔为24h，每分钟小于10ml，给药间隔为24～36h。
药物相应作用
1.本药与氟胞嘧啶同用可增强两者药效，但也可增强氟胞嘧啶的毒性反应，因本药可增加细胞摄取氟胞嘧啶并减少其自肾排泄。
2.肾上腺皮质激素：此类药物除在控制两性霉素B的药物反应时可合用外，一般不推荐两者同时应用，因为由两性霉素B诱发的低钾血症有可能被肾上腺皮质激素类药物加重，如需同用时则后者宜给于最小剂量和最短疗程，并需监测患者的血钾浓度和心脏功能。
3.洋地黄苷：两性霉素B应用时可能发生的低钾血症，可增强潜在的洋地黄毒性反应，两者同用时应经常监测血钾浓度和心脏功能。
4.肾毒性药物：如氨基糖苷类、抗肿瘤药、卷曲霉素、多黏菌素类、万古霉素与两性霉素B同用时肾毒性增强。
5.由两性霉素B诱发的低钾血症可增强神经肌肉阻断药的作用，因此两者同用时应经常测定患者的血钾浓度。
6.同时应用尿液碱化药可增加两性霉素B的排泄，并防止或减少肾小管酸中毒发生的可能。
临床研究
本品为抗深部真菌感染药，对常见致病真菌有较强抗菌作用。本品静脉滴注可有严重反应，用药前需给解热镇痛药，抗组胺药物和适量可的松以减少全身反应。毒性较大。
通过回顾性调查，比较两性霉素B或氟康唑联合5-FC对隐球菌脑膜炎疗效和副作用，了解治愈率、脑脊液隐球菌转阴时间及不良反应的差异。两性霉素B联合5-FC治疗组治愈率为33%，总有效率为74%，脑脊液隐球菌转阴时间中位数为88天；氟康唑联合5-FC治疗组治愈率为47%，总有效率为88%，脑脊液隐球菌转阴时间中位数为71.5天。两性霉素B＋5-FC组不良反应主要有发热、寒战(88%)、低血钾症(84%)、肝脏损害(63%)、肾脏损害(42%)、心脏损害(21%)、血液系统损害(28%)、消化道症状(51%)和神经系统毒性(7%)；而在氟康唑＋5-FC治疗组中，肝脏损害发生率(18%)比两性霉素B＋5-FC组低，未见其他不良反应发生。两性霉素B联合5-FC治疗隐球菌性脑膜炎时中毒性肝炎的发生率高，但不引起严重的中毒性肝损害。对肾脏的毒性表现为氮质血症，尿毒症的发生率低。
保质期
2年
包装规格
50毫克/小瓶
生产厂家：E. R. Squibb & Sons Limited

Fungizone 50mg Powder for Sterile Concentrate
1. Name of the medicinal product
Fungizone 50 mg Powder for Sterile Concentrate
2. Qualitative and quantitative composition
Each vial contains amphotericin B 50,000 units (50 mg).
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder for Concentrate for Solution for Infusion (Powder for Sterile Concentrate).
Fungizone powder is a fine yellow to orange fluffy powder.
4. Clinical particulars
4.1 Therapeutic indications
Fungizone should be administered primarily to patients with progressive, potentially fatal infections. This potent drug should not be used to treat the common forms of fungal disease which show only positive skin or serological tests.
Fungizone is specifically intended to treat cryptococcosis (torulosis); North American blastomycosis; the disseminated forms of candidosis, coccidioidomycosis and histoplasmosis; mucormycosis (phycomycosis) caused by species of the genera Mucor, Rhizopus, Absidia, Entomophthora, and Basidiobolus sporotrichosis (Sporotrichum schenckii), aspergillosis (Aspergillus fumigatus).
Amphotericin B may be helpful in the treatment of American mucocutaneous leishmaniasis but is not the drug of choice in primary therapy.
4.2 Posology and method of administration
Adults and children:
Fungizone should be administered by intravenous infusion over a period of 2-4 hours. Reduction of the infusion rate may reduce the incidence of side-effects. In rare instances infusion times of up to 6 hours may be necessary. Initial daily dose should be 0.25 mg/kg of body weight gradually increasing to a level of 1.0 mg/kg of body weight depending on individual response and tolerance. Within the range of 0.25-1.0 mg/kg the daily dose should be maintained at the highest level which is not accompanied by unacceptable toxicity.
In seriously ill patients the daily dose may be gradually increased up to a total of 1.5 mg/kg. Since amphotericin B is excreted slowly, therapy may be given on alternate days in patients on the higher dosage schedule. Several months of therapy are usually necessary; a shorter period of therapy may produce an inadequate response and lead to relapse.
When commencing all new courses of treatment, it is advisable to administer a test dose immediately preceding the first dose. A volume of the infusion containing 1 mg (i.e. 10 mL) should be infused over 20-30 minutes and the patient carefully observed for at least a further 30 minutes. It should be noted that patient responses to the test dose may not be predictive of subsequent severe side effects.
Whenever medication is interrupted for a period longer than seven days, therapy should be resumed by starting with the lowest dosage level, i.e. 0.25 mg/kg of body weight and increased gradually.
Safety and effectiveness in paediatric patients have not been established through adequate and well-controlled studies. Systemic fungal infections have been treated in paediatric patients, with reports of side effects similar to those seen in adults (see section 4.8).
CAUTION:
Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded. Amphotericin B overdoses can result in potentially fatal cardiac or cardiorespiratory arrest (see section 4.4 & 4.9). The recommended concentration for intravenous infusion is 10 mg/100mL.
Elderly:
No specific dosage recommendations or precautions.
The use of Fungizone by other routes has been documented in the published literature:
Bladder irrigation/instillation (e.g. candiduria): Continuous irrigation with 50 mg Fungizone in 1 litre sterile water each day until urinary cultures are negative. Intermittent use of volumes of 100-400 mL (concentrations of 37.5-200 mcg/mL) has also been reported. The urine should be alkalinised (with potassium citrate) and antifungal ointment applied to the perineal area.
Lung inhalation (e.g. pulmonary aspergillosis): 8-40 mg amphotericin B (nebulised in sterile water or 5% Glucose) has been given daily in divided doses. Concurrent eradication of oral and intestinal yeast reservoirs is recommended.
Intrathecal (e.g. coccidiodal meningitis): Patients who do not respond to fluconazole or itraconazole would be candidates for intrathecal amphotericin B therapy with or without continuation of azole treatment. The intrathecal dosage of amphotericin B normally ranges between 0.1mg and 1.5mg per dose, administered at intervals ranging from daily to weekly, beginning at a low dosage and increasing the dosage until the appearance of patient intolerance. Amphotericin B is irritating when injected into the CSF.
Other: Other uses of solutions prepared using Fungizone include local instillations for the treatment of fungal infections of the ear, eye, peritoneum, lung cavities and joint spaces.
Method of administration: For instructions on reconstitution of the medicinal product before administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substance unless, in the opinion of the physician, the condition requiring treatment is life-threatening and amenable only to such therapy , or to any of the excipients listed in section 6.1,.
4.4 Special warnings and precautions for use
Prolonged therapy with amphotericin B is usually necessary. Unpleasant reactions are quite common when the drug is given parenterally at therapeutic dosage levels. Some of these reactions are potentially dangerous. Hence amphotericin B should be used parenterally only in hospitalised patients, or those under close clinical observation. If serum creatinine exceeds 260 micromol/L the drug should be discontinued or the dosage markedly reduced until renal function is improved. Weekly blood counts and serum potassium determinations are also advisable. Low serum magnesium levels have also been noted during treatment with amphotericin B. Therapy should be discontinued if liver function test results (elevated bromsulphalein, alkaline phosphatase and bilirubin) are abnormal.
Leucoencephalopathy has been reported very occasionally following the use of amphotericin B injection in patients who received total body irradiation. Most of these patients received high cumulative doses of amphotericin B.
Rapid intravenous infusion, over less than one hour, particularly in patients with renal insufficiency, has been associated with hyperkalaemia and arrhythmias and should therefore be avoided.
Corticosteroids should not be administered concomitantly unless they are necessary to control drug reactions. Other nephrotoxic antibiotics and antineoplastic agents should not be given concomitantly except with great caution.
Care must be taken when administering Fungizone to prevent overdose, which can result in potentially fatal cardiac or cardiorespiratory arrest. Verify the product name and dosage pre-administration, especially if the dose prescribed exceeds 1.5 mg/kg (see section 4.2 & 4.9).
4.5 Interaction with other medicinal products and other forms of interaction
Concomitant administration of nephrotoxic drugs or antineoplastics should be avoided if at all possible.
The hypokalaemia following amphotericin B therapy may potentiate the toxicity of digitalis glycosides or enhance the curariform actions of skeletal muscle relaxants.
Corticosteroids and Corticotrophin (ACTH) may increase the potassium loss due to amphotericin B.
Flucytosine toxicity may be enhanced during concomitant administration, possibly due to an increase in its cellular uptake and/or impairment of its renal excretion.
Acute pulmonary reactions have occasionally been observed in patients given amphotericin B during or shortly after leukocyte transfusions. It is advisable to separate these infusions as far as possible and to monitor pulmonary function.
4.6 Fertility, pregnancy and lactation
Pregnancy
Safety for use in pregnancy has not been established; therefore it should be used during pregnancy only if the possible benefits to be derived outweigh the potential risks involved.
Lactation
It is not known whether amphotericin B is excreted in human milk. As excretion of amphotericin B in human milk is possible, and considering its potential toxicity, it should be used in nursing mothers only if the possible benefits to be derived outweigh the potential risks involved. In addition , it is prudent to advise a nursing mother to discontinue nursing.
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
While some patients may tolerate full intravenous doses of amphotericin B without difficulty, most will exhibit some intolerance particularly during the initiation of therapy. In patients experiencing adverse reactions these may be made less severe by giving aspirin, other antipyretics, antihistamines or anti-emetics. Pethidine (25 to 50 mg IV) has been used in some patients to decrease the duration or intensity of shaking chills and fever following amphotericin B therapy. Febrile reactions may be decreased by the intravenous administration of small doses of adrenal corticosteroids, e.g. 25 mg hydrocortisone. This may be administered just prior to or during amphotericin B infusion. The dosage and duration of such corticosteroid therapy should be kept to a minimum. Administration of the drug on alternate days may decrease anorexia and phlebitis. Adding a small amount of heparin (1000 units per infusion) to the infusion, rotation of the injection site, the use of a paediatric scalp-vein needle and alternate day therapy may lessen the incidence of thrombophlebitis and coagulation problems. Extravasation may cause chemical irritation.
The table below lists all adverse events. The list is presented by system organ class and frequency, which 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), very rare (<1/10,000), and not known (cannot be estimated from the available data).

System Organ Class	Frequency	Adverse Event (MedDRA)
Blood and Lymphatic System Disorders	Common	Anaemia
	Not known	Agranulocytosis, coagulopathy, eosinophilia, leukocytosis, leukopenia and thrombocytopenia
Cardiac Disorders	Not known	Arrhythmias, including ventricular fibrillation, cardiac arrest and cardiac failure
Ear and Labyrinth Disorders	Not known	Deafness, tinnitus and vertigo
Eye Disorders	Not known	Blurred vision, diplopia
Gastrointestinal Disorders	Very common	Nausea, vomiting
	Not known	Dyspepsia, haemorrhagic gastroenteritis, abdominal pain upper, diarrhoea, melena
General Disorders and Administration Site Conditions	Very common	Chills (usually occurring within 15 to 20 minutes after initiation of treatment), pyrexia
	Uncommon	Flushing
	Not known	Pain, malaise and injection site pain with or without phlebitis or thrombophlebitis
Hepatobiliary Disorders	Common	Abnormal hepatic function
	Not known	Acute liver failure, jaundice, liver function test abnormalities
Immune System Disorders	Not known	Anaphylactoid/anaphylactic reactions
Investigations	Very common	Hypokalaemia, increased blood creatinine
	Not known	Hyperkalaemia, weight decreased
Metabolism and Nutrition Disorders	Common	Hypomagnesemia
	Not known	Anorexia
Musculoskeletal and Connective Tissue Disorders	Not known	Arthralgia, myalgia
Nervous System Disorders	Not known	Convulsions, headache, encephalopathy, neurologic symptoms, and neuropathy peripheral
Renal and Urinary Disorders	Very common	Renal function test abnormalities includes*: azotemia, hyposthenuria, renal tubular acidosis, and nephrocalcinosis,
	Not known	Renal failure acute, anuria, nephrogenic diabetes insipidus, oliguria, renal insufficiency and renal impairment
Respiratory, Thoracic and Mediastinal Disorders	Very common	Dyspnoea
	Not known	Alveolitis allergic, bronchospasm, non-cardiogenic pulmonary edema
Skin and Subcutaneous Tissue Disorders	Common	Rash
	Not known	Rash maculopapular, pruritus, skin exfoliation, toxic epidermal necrolysis, Stevens-Johnson syndrome
Vascular Disorders	Very common	Hypotension
	Not known	Hypertension; shock

is also commonly observed and usually improves upon interruption of therapy; however, some permanent impairment often occurs, especially in those patients receiving large cumulative amounts (over 5 g) of amphotericin B. Concomitant diuretic therapy may be a predisposition for renal impairment, whereas sodium repletion or supplementation may reduce the occurrence of nephrotoxicity.
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 at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Amphotericin B overdoses can result in potentially fatal cardiac or cardio-respiratory arrest. If an overdose is suspected, discontinue therapy and monitor the patient's clinical status (e.g cardio-respiratory, renal, and liver function, haematologic status serum electrolytes) and administer supportive therapy as required. Amphotericin B is not haemodialysable. Prior to reinstituting therapy, the patient's condition should be stabilised (including correction of electrolyte deficiencies, etc.).
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-infectives for systemic use , ATC code: J02AA01
Amphotericin B is a polyene antifungal antibiotic active against a wide range of yeasts and yeast-like fungi including Candida albicans. Crystalline amphotericin B is insoluble in water; therefore, the antibiotic is solubilised by the addition of sodium desoxycholate to form a mixture which provides a colloidal dispersion for parenteral administration. Amphotericin B is fungistatic rather than fungicidal in concentrations obtainable in body fluids. It probably acts by binding to sterols in the fungal cell membrane with a resultant change in membrane permeability which allows leakage of intracellular components. Mammalian cell membranes also contain sterols and it has been suggested that the damage to human and fungal cells may share common mechanisms. No strains of Candida resistant to amphotericin B have been reported in clinical use, and although in vitro testing does produce a small number of resistant isolates this occurs only following repeated subcultures.
5.2 Pharmacokinetic properties
An initial intravenous infusion of 1 to 5 mg of amphotericin B per day, gradually increased to 0.65 mg/kg daily, produces peak plasma concentrations of approximately 2 to 4 mg/L which can persist between doses since the plasma half-life of amphotericin B is about 24 hours. It has been reported that amphotericin B is highly bound (more than 90%) to plasma proteins and is poorly dialysable.
Amphotericin B is excreted very slowly by the kidneys with 2 to 5% of a given dose being excreted in biologically active form. After treatment is discontinued the drug can be detected in the urine for at least seven weeks. The cumulative urinary output over a seven day period amounts to approximately 40% of the amount of drug infused.
Details of tissue distribution and possible metabolic pathways are not known.
5.3 Preclinical safety data
No further relevant data.
6. Pharmaceutical particulars
6.1 List of excipients
Other ingredients: desoxycholic acid, concentrated phosphoric acid, sodium hydroxide, disodium phosphate dodecahydrate, monosodium phosphate dehydrate.
6.2 Incompatibilities
Do not reconstitute with saline solutions. The use of any diluent other than the ones recommended or the presence of a bacteriostatic agent in the diluent may cause precipitation of the amphotericin B
6.3 Shelf life
2 years
The concentrate (5 mg per ml after reconstitution with 10 mL sterile Water for Injections) should be stored protected from light. The absence of any antimicrobial preservative and the risk of contamination during reconstitution mean that the product should be stored for no more than 8 hours at room temperature (25°C) or 24 hours in a refrigerator (2-8°C). Should the need arise and a validated aseptic reconstitution technique is applied, the product is chemically stable when stored for 24 hours at room temperature or one week in a refrigerator. It is not intended as a multidose vial. Any unused material should be discarded. Solutions prepared for intravenous infusion (i.e. 10 mg or less amphotericin B per 100 mL) should be used promptly after preparation.
6.4 Special precautions for storage
Vials of powder for reconstitution should be stored in a refrigerator.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
Type I flint glass vials closed with a grey chlorobutyl rubber stopper.
Vials of 50 mg.
6.6 Special precautions for disposal and other handling
Preparation of solutions:
Reconstitute as follows: An initial concentrate of 5 mg amphotericin B per ml is first prepared by rapidly expressing 10 mL sterile water for injection, without a bacteriostatic agent, directly into the lyophilised cake, using a sterile needle (minimum diameter: 20 gauge) and syringe. Shake the vial immediately until the colloidal solution is clear. The infusion solution, providing 10 mg/100 mL is obtained by further dilution (1:50) with 5% Glucose Injection of pH above 4.2. The pH of each container of Glucose Injection should be ascertained before use. Commercial Glucose Injection usually has a pH above 4.2; however, if it is below 4.2 then 1 or 2 ml of buffer should be added to the Glucose Injection before it is used to dilute a concentrated solution of amphotericin B. The recommended buffer has the following composition:
Dibasic sodium phosphate (anhydrous)  1.59 g
Monobasic sodium phosphate (anhydrous)  0.96 g
Water for Injections BP  q.s. to 100 mL
The buffer should be sterilised before it is added to the Glucose Injection, either by filtration through a bacterial filter, or by autoclaving for 30 mins at 15 lb pressure (121°C).
CAUTION:
Aseptic technique must be strictly observed in all handling, since no preservative or bacteriostatic agent is present. Do not use the initial concentrate or the infusion solution if there is any evidence of precipitation of foreign matter.
An in-line membrane filter may be used for intravenous infusion of amphotericin B; however the mean pore diameter of the filter should not be less than 1.0 micron in order to assure passage of the amphotericin B dispersion.
Other preparations for injection should not be added to the infusion solution or administered via the cannula being used to administer Fungizone.
Aseptic technique must be strictly observed during the preparation of the concentrate, the buffer and the infusion.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
E. R. Squibb & Sons Limited
Uxbridge Business Park
Sanderson Road
Uxbridge
Middlesex UB8 1DH
8. Marketing authorisation number(s)
PL 0034/5041R
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation:01 September 1971
Date of latest renewal: 27 October 2010
10. Date of revision of the text
May 2014