21．大扶康
出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第77页（22780字）
【中文释文】：
(氟康唑)
〔性状〕
氟康唑为双三唑化合物，化学式为：2-(2，4-二氟苯基)-1，3-双(1H-1，2，4-三唑-1-基)-2-丙醇。
氟康唑为白色至米白色结晶粉末，微溶于水及盐水溶液。分子量为306．3。
氟康唑之规格分为：50mg或150mg氟康唑胶囊及每毫升盐水含2mg氟康唑(2mg／rnl)之静脉滴注液。
〔药理作用〕
氟康唑为新型三唑类抗真菌药，能强力而特异地抑制真菌的甾醇合成。
口服及静脉注射氟康唑，对多种动物真菌感染有效。已证明对条件致病真菌感染有效，如念珠菌属感染，包括全身性念珠菌病及动物因免疫受抑制而引起的感染；新型隐球菌感染，包括颅内感染；小孢子菌属感染，及毛癣菌属感染。亦证明氟康唑对动物之局部真菌病有效，包括皮炎芽生菌感染；粗球孢子菌感染，包括颅内感染；和正常及免疫受抑制动物的荚膜组织胞浆菌感染。
氟康唑口服和静脉注射的药动学性质相似。口服氟康唑后吸收良好，血药浓度(及全身的生物利用度)可达静脉注射后血药浓度的90%以上。口服吸收不受同时摄入的食物影响。空腹服用氟康唑后0．5～1．5h，血药浓度达到峰值，血浆消除半衰期约为30h。血药浓度与剂量成比例。每日给药1次连续给药至第4～5d，血药浓度已达稳态浓度的90%。
第1d给予负荷剂量即给予常规日剂量的2倍，第2d血药浓度即可接近稳态水平的90%。表观分布容积接近于体内水的总量。血浆蛋白结合率很低(11%～12%)。
氟康唑能良好地透入全身体液。氟康唑在唾液和痰中的浓度接近血药浓度。在真菌性脑膜炎病人的脑脊髓液中，氟康唑的浓度约为相应血药浓度的80%。
氟康唑大部经肾排出，所给剂量的80%以原型随尿排泄。氟康唑的清除率与肌酐清除率成比例。循环中未发现代谢物。
因氟康唑的血浆消除半衰期长，使其仅需给药一次，便可治疗阴道念珠菌病。而治疗其他真菌感染时，每日亦只需给药一次。
氟康唑对真菌的细胞色素P-450依赖酶的具有高度特异性。已证明服用氟康唑50mg／d，连续服用至第28d，对男性的血浆睾丸素浓度及育龄期妇女的甾类浓度均无影响。与安替比林相互作用研究显示，无论是服用氟康唑50mg单剂量或多剂量，皆不会影响安替比林的代谢。
〔适应证〕
氟康唑可治疗以下各种感染：
1．隐球菌病，包括稳球菌脑膜炎及其他部位之感染(如肺，皮肤)。亦可治疗正常宿主，艾滋病人，器官移植或其他原因而引起免疫抑制的病人。艾滋病病人可服用氟康唑作维持治疗，以预防隐球菌病复发。
2．全身性念珠菌病，包括念珠菌血症，播散性念珠菌病，及其他非浅表性念珠菌感染。这些感染包括腹膜，心内膜，肺部及尿路的感染。患有恶性肿瘤而在重症监护病房内接受细胞毒或免疫抑制治疗的病人，或有发生念珠菌感染倾向的病人，亦可用氟康唑来治疗。
3．粘膜念珠菌病，包括口咽，食管，非侵入性肺支气管感染，念珠菌尿症，皮肤粘膜及慢性口腔萎缩性念珠菌病(口腔义齿溃疡)。正常宿主及免疫功能受损之病人，皆可用氟康唑治疗。
4．急性及复发性阴道念球菌病。
5．对于那些因接受细胞毒化疗或放疗，而容易受感染的恶性肿瘤病人，氟康唑可用来作预防真菌感染。
6．脚癣，体癣，股癣，花斑癣和皮肤念珠菌感染。氟康唑不适用于甲癣。
〔禁忌证〕
对氟康唑或其他三唑类药物过敏的病人，禁忌使用氟康唑。
〔警惕〕
极少数病人，服用多次剂量氟康唑后，因严重潜伏性疾病死亡，而在尸检结果中显示有肝坏死。不过，这些病人同时接受其他药物治疗，部分药物已知具有潜在的肝毒性和／或引发能导致肝坏死的潜伏性疾病。因此，引致死亡原因与氟康唑之关系尚未明确。故若病人的肝酶有明显上升时，须衡量继续氟康唑治疗的利害关系。
〔注意事项〕
1．妊娠期使用 妊娠期妇女使用氟康唑的病例很少。在动物试验中，只发现与母体的毒性有关的高剂量对胎儿有不良反应，但这结果不表示与服用治疗剂量氟康唑的结果有关。不过，妊娠期妇女应避免使用此药，除非病者患有严重或可致命的真菌感染，而且预期所获的疗效较可能出现对胎儿之危害为大时，氟康唑或可考虑使用。
2．哺乳期使用 尚未有关于乳汁中氟康唑浓度的数据，故不推荐哺乳期妇女使用。
3．儿童服用 关于氟康唑使用于16岁以下儿童的数据十分有限，故暂不推荐使用在这些病儿中，除非抗真菌感染之治疗十分迫切而又没有其他合适的替代药物。关于氟康唑用于新生儿的数据目前尚无，故不推荐氟康唑使用于1岁以下的婴儿。
4．驾驶／机械操作 从服用氟康唑所得之经验显示，此药不影响病人驾驶或操作机械的能力。
〔药物相互作用〕
在一药物相互作用试验中，正常男性服用华法令后，氟康唑能延长凝血酶原时间。虽然所增加的幅度很小(12%)，但仍建议，对于并用双香豆素类抗凝药物的病人，应仔细监测凝血酶原时间。
在正常人中，氟康唑延长同时，服的磺脲类药物(氯磺丙脲，优降糖，吡磺环已脲及甲糖宁)的血清半衰期。对于糖尿病病人，氟康唑与口服磺脲类药物可同时服用，但要注意可能出现低血糖反应。在药物动力学相互作用试验中，同时服用多剂量双氢氯噻嗪及氟康唑的正常人，其氟康唑的血药浓度增加40%。对于同时服用利尿剂的病人而言，有增幅之效果，虽然不一定要调节氟康唑的剂量，但医生需加以留意。
同时服用氟康唑及苯妥英，可使苯妥英血药浓度增加至临床上有意义的程度。如两者要同时服用，须监测苯妥英血药浓度并调节其剂量至维持治疗水平。
氟康唑多剂量的药代动力学相互作用研究显示：50mg／d不影响女性内源性类固醇浓度或口服避孕药之药代动力学；100mg／d不会影响骨髓移植病人的环孢菌素浓度；200～400mg／d不会影响正常男性内源性类固醇浓度或ACTH功能。这些结果亦适用于单剂量150mg。
相互作用研究显示，当氟康唑与食物，甲氰咪胍，制酸剂同服时，或进行骨髓移植全身辐照射后，氟康唑的吸收没有具有临床意义的减弱。
同时服用氟康唑及利福平，会使氟康唑的AUC减少25%，且氟康唑的半衰期缩短20%。对于同时服用利福平的病人，应考虑增加氟康唑的剂量。
〔不良反应〕
一般而言，人对氟康唑的耐受性良好。最常见的副作用与胃肠道症状有关，包括恶心，腹痛，腹泻及胃肠胀气。除此之外，另一常见之副作用为皮疹。某些病人，特别是那些具严重疾病的病人，如艾滋病及肿瘤病人，在接受氟康唑及其他类似药物治疗时，可能出现肾及血液学功能的改变及肝脏异常(见警惕)，但其临床意义与氟康唑治疗之关系尚未明了。
很多药物都会令艾滋病病人产生严重皮肤反应。少数艾滋病病人，同时服用氟康唑和已知可引起严重剥脱性皮炎之其他药物，可出现严重皮肤反应。如认为病人在治疗口腔念珠菌病时所出现的皮疹与氟康唑有关，应停止使用本药。应严密观察非浅表性／全身性真菌感染病人所出现之皮疹，如发现大疱损害或多形红斑，应停止使用氟康唑。
〔剂量及用法〕
氟康唑可以口服或以不超过10ml／min的速度静脉滴注，选用何种服法，根据病人的临床状况而定。由静脉滴注转为口服，或相反途径，氟康唑的每日剂量不需要改变。氟康唑以0．9%氯化钠溶液配制而成，每200mg(100ml玻璃瓶)含Na+及Cl-各15mmol。因氟康唑注射剂为稀盐水溶液，故对限制钠或液体的病人，应考虑输液速率。氟康唑静脉滴注液可与下列溶液配伍：
20%葡萄糖；
林格溶液；
哈特曼溶液；
氯化钾葡萄糖溶液；
4．2%碳酸氢钠；
Aminofusin(一种氨基酸输液)；
生理盐水。
氟康唑可与上列溶液用同一输液管滴注。虽然尚未发现配伍禁忌，但仍不建议在滴注前与其他药物混合。
一、成人
1．治疗隐球菌脑膜炎及其他部位隐球菌感染，常用剂量为首日400mg，随后每天1次200～400mg。治疗隐球菌感染的疗程，取决于临床及真菌反应，但对于隐球菌脑膜炎而言，一般治疗期最少为6～8周。为防止艾滋病病人隐球菌脑膜炎复发，在病人接受整个疗程的基本治疗后，可无限期地给予氟康唑，至少100mg／d。
2．治疗念珠菌血症，播散性念珠菌病及其他非浅表性念珠菌感染时，常用剂量为第1d400mg，然后200mg／d。根据临床反应，可将剂量增至400mg／d，每天1次。治疗期长短取决于临床反应。
3．治疗口咽部念珠菌病常用剂量为50mg／d，给药7～14d。对免疫功能严重损害的病人，可延长疗程。与义齿有关的萎缩性口腔念珠菌病，常用剂量为50mg／d，每天1次，连用14d，同时义齿部位给予局部抗菌药。
治疗其他粘膜念珠菌病(除阴道念珠菌病，见下项)，如食管，非侵入性肺支气管感染，念珠菌尿症，皮肤粘膜念珠菌病等，常用有效剂量为50mg／d，每天1次，给药14～30d。
对于异常难治的粘膜念珠菌感染，剂量可增加至100mg／d，每天1次。
4．对阴道念珠菌感染，口服氟康唑150mg，每天1次。
5．对接受化疗或放疗而容易感染的恶性肿瘤病人，预防剂量为50mg／d，每天1次。
6．对于足癣、体癣，股癣和花斑癣及皮肤念珠菌感染，推荐剂量为50mg，每天1次，治疗时间通常为2～4周，但足癣要求6周，治疗时间不应超过6周。
二、儿童
如在注意事项内所述，对于16岁以下儿童，不建议使用氟康唑。但如认为必须用氟康唑治疗时，则建议1岁以下而肾功能正常儿童之日常剂量：浅表念珠菌感染为1～2 mg／kg，全身念珠菌／隐球菌感染为3～6mg／kg。
对肾功能不全的儿童，氟康唑日常剂量要按照成人的原则，予以减少，减少的程度按肾功能而定。
三、老年人
没有肾功能不全者，可服用上述所建议的成人正常剂量。对于肾功能不全者(肌酐清除率＜40ml／min)，则应按下述来调节剂量。
四、肾功能不全病人
大部分氟康唑随尿液以原型排泄，只需给药1次之治疗，不用调节剂量。需多次给药时，第1d及第2d应给常规剂量，此后应按肌酐清除率来调节给药的间隔时间或日常剂量，如下列所述：
肌酐清除率(ml／min) 给药的间隔时间／日常剂量
＞40 24h(常规剂量)
21～40 48h或常规剂量的一半
10～20 72h或常规剂量的1／3
进行常规透析的病人 每次透析后给药一次
〔给药过量〕
给药过量时，应充分给予对症治疗(支持疗法，必要时应洗胃)。
由于氟康唑大多随尿液排泄，故可增加尿量以加快清除速率。血液透析3h，可使血药浓度降低约50%。
大扶康*乃辉瑞公司注册商标。
〔生产厂家〕
美国辉瑞有限公司
(附本品别名：麦道氟唑，medoflcon)
【外文释文】：
Brand of fluconazole
Description
Fluconazole is a bis-triazole：
2-(2，4-difluoropheny 1)-1，3-bis(1H-1，2，4-triazol-1-y1)-2-propanol．
Fluconazole is a white to off-white crystalline powder which is sparingly soluble in water and saline．It has a molecular weight of 306．3．
Fluconazole is available as gelatin capsules containing 50mg，or 150 mg fluconazole，an intravenous infusion containing fluconazole 2 mg／ml in a saline solution．
Actions
Fluconazole，a member of a new class of triazole antifungal agents，is a potent and specific inhibitor of fungal steroid synthesis．Both orally and intravenously adminstered fluconazole was active in a variety of animal fungal infection models．Activity has been demonstrated against opportunistic mycoses，such as infections with Candida spp，including systemic candidiasis and in immunocompromised animals；with Cryptococcus neoformans，including intracranial infections；with Microsporum spp；and with Trichophyton spp．Fluconazole has also been shown to be active in animal models of endemic mycoses，including infections with Blastomyces dermatitidis；with Coccidioides immitis，including intracranial infection；and with Histoplasma capsulatum in normal and immunosuppressed animals．
The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral route．After oral administration fluconazole is well absorbed，and plasma levels(and systemic bioavailability)are over 90% of the levels achieved after intravenous administration．Oral absorption is not affected by concomitant food intake．Peak plasma concentrations in the fasting state occur between 0．5-1．5 hours post-dose with a plasma elimination half-life of approximately 30 hours．Plasma concentrations are proportional to dose．Ninety percent steady-state levels are reached by 4-5 with multiple once daily dosing．
Administration of loading dose(on day 1)of twice the usual daily dose enables plasma levels to approximate to 90% steady-state levels by day 2．The apparent volume of distribution approximates to total body water．Plasma protein binding is low(1 1%-12%)．
Fluconazole achieves good penetration into all body fluids studied．The levels of fluconazole in saliva and sputum are similar to plasma levels．In patients with fungal meningitis，fluconazole levels in the CSF are approximately 80%the corresponding plasma levels．
The major route of excretion is renal，with approximately 80%of the administered dose appearing in the urine as unchanged drug．Fluconazole clearance is proportional to creatinine clearance．There is no evidence of circulating metabolites．
The long plasma elimination half-life provides the basis for single dose therapy for vaginal candidiasis and once daily dosing for all other indications．
Fluconazole is highly specific for fungal cytochrome P-450 dependent enzymes．Fluconazole 50 mg daily given up to 28 days has been shown not to affect testosterone plasma concentrations in males or steroid concentrations in females of child-bearing age．Interaction studies with antipyrine indicate that single or multiple doses of fluconazole 50 mg do not affect its metabolism．
Indications
Fluconazole is indicated for the treatment of the following conditions：
1．Cryptococcosis，including cryptococcal meningitis and infections of other sites(e．g． pulmonary，cutaneous)．Normal hosts and patients with AIDS，organ transplants or other causes of immunosuppression may be treated．Fluconazole can be used as maintenance therapy to prevent relapse of cryptococcal disease in patients with AIDS．
2．Systemic candidiasis，including candidemia，disseminated candidiasis and other forms of invasive candidal infection．These include infections of the peritoneum，endocardium and pulmonary and urinary tracts．Patients with malignancy，in intensive care units，receivingcytotoxic or immunosuppressive therapy，or with other factors predisposing to candidal infection may be treated．
3．Mucosal candidiasis．These include oropharyngeal，esophageal，non-invasive bronchopulmonary infections，candiduria，mucocutaneous and chronic oral atrophic candidiasis(denture sore mouth)．Normal hosts and patients with compromised immune function may be treated．
4．Vaginal candidiasis，acute or recurrent．
5．Prevention of fungal infection in patients with malignancy who are predisposed to such infections as a result of cytotoxic chemotherapy or radiotherapy．
6．Tinea pedis，tinea corporis，tinea cruris，tinea versicolor and dermal candidal infections．Diflucan is not indicated for nail infections．
Contraindications
Fluconazole should not be used in patients with known sensitivity to the drug or to related triazole compounds．
Warnings
Very rarely patients who died with severe underlying disease and who had received multiple dose fluconazole had post mortem findings which included hepatic necrosis．These patients were receiving multiple concomitant medications，some known to be potentially hepatotoxic and／or had underlying diseases which could have caused the hepatic necrosis．Consequently，because a causal relationship with fluconazole can not be excluded，in those patients in whom a significant rise of liver enzymes occurs，the risk-benefit ratio of continued fluconazole treatment should be assessed．
Precautions
Use during pregnancy
There has been little use of fluconazole during pregnancy in humans．Adverse fetal effects have been seen in animals only at high dose levels associated with maternal toxicity．These findings are not considered relevant to fluconazole used at therapeutic doses．However，use in pregnancy should be avoided except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the anticipated benefit outweightsthe possible risk the fetus．
Use during lactation
No data concerning fluconazole levels in breast milk are available，hence its use in nursing mothers is not recommended．
Use in children
Limited data are available on the use of fluconazole in children below the age of 16 years；therefore，use at present is not recommended in these patients unless antifungal treatment is imperative and no suitable alternative agents exist．There are no available data on the use of fluconazole in neonates，and its use in children below the age of 1 year is therefore not recommended．
Driving／use of machinery
Experience with fluconazole indicates that therapy is unlikely to impair a patient’s ability to drive or use machinery．
Drug Interactions
In an interaction study，fluconazole increased the prothrombin time after warfarin administration in healthy males．Though the magnitude of change was small(12%)，careful monitoring of prothrombin time in patients receiving coumarin-type anticoagulants is recommended．
Fluconazole has been shown to prolong the serum half-life of concomitantly administered oral sulfonylureas(chlorpropamide，glibenclamide，glipizide and tolbutamide)in healthy volunteers．Fluconazole and oral sulfonylureas may be co-administered to diabetic patients，but the possibility of a hypoglycemic episode should be borne in mind．
In a kinetic interaction study，co-administration of multiple-dose hydrochlorothiazide to healthy volunteers receiving fluconazole increased plasma concentrations of fluconazole by 40%．An effect of magnitude should not necessitate a change in the fluconazole dose regimen in subjects receiving concomitant diuretics，although the prescriber should bear it in mind．
Concomitant administration of fluconazole and phenytoin may increase the levels of phenytoin to a clinically significant degree．If it is necessary to administer both drugs concomitantly，phenytoin levels should be monitored and the phenytoin dose adjusted to maintain therapeutic levels．
Kinetic interaction studies with multiple-dose fluconazole have shown the following：50 mg daily does not affect endogenous steroid levels or the kinetics of the oral contraceptive in females；100 mg daily does not affect cyclosporin levels in patients with bone marrow transplants；200-400 mg daily has no clinically significant effect on endogenous steroid levels or on ACTH stimulated response in healthy male volunteers．These conclusions are also applicable to a 150 mg single dose．
Interaction studies have shown that when oral fluconazole is co-adminstered with food，cimetidine，antacids or following total body irradiation for bone marrow transplantation，no clinically significant impairment of fluconazole absorption occurs．
Concomitant administration of fluconazole and rifampicin resulted in a 25%decrease in the AUC and 20%shorter half-life of fluconazole．In patients receiving concomitant rifampicin，an increase of the fluconazole dose should be considered．
Adverse reactions
Fluconazole is generally well tolerated．The commonest side effects associated with fluconazole are symptoms related to the gastrointestinal tract．These include nausea，abdominal pain，diarrhea and flatulence．After gastrointestinal symptoms，the second most commonly observed side effect was rash．In some patients，particularly those with serious underlying diseases such as AIDS and cancer，changes in renal and hematological function test results and hepatic abnormalities(see Warnings)have been observed during treatment with fluconazole and comparative agents，but the clinical significance and relationship to treatment is uncertain．
Patients with AIDS are more prone to the development of severe cutaneous reactions to many drugs．A small number of AIDS patients have develcped such reactions，usually while receiving fluconazole concomitantly with other agents known to be associated with exfoliative cutaneous reactions．If a rash develops in a patient treated for oral candidiasis which is considered attributable to fluconazole，further therapy with this agent should be discontinued．In patients with invasive／systemic fungal infections who develop rashes，they should be monitored closely and fluconazole discontinued if bullous lesions or erythema multiforme develop．
Dosage and administration
Fluconazole may be administered either orally or by intravenous infusion at a rate not exceeding 10 ml／minute，the route being dependent on the clinical state of the patient．On transferring from the intavenous to the oral route or vice versa，there is no need to change the daily dosage．Fluconazole is formulated in 0．9% sodium chloride solution，each 200 mg(100 ml bottle)containing 15mmol each of Na+and C1-．Because fluconazole is avaiable as a dilute，in patients requiring sodium or fluid restriction，consideration should be given to the rate of fluid administration．Fluconazole intravenous infusion is compatible with the following administration fluids：
·Dextrose 20%
·Ringer’s solution
·Hartmann’s solution
·Potassiun chloride in dextrose
·Sodium bicarbonate 4．2%
·Aminofusin
·Normal saline
Fluconazole may be infused through an existing line with one of the above listed fluids．Although no specific incompatibilities have been noted，mixing with any other drug prior to infusion is not recommended．
·In Adults
1．For cryptococcal meningitis and cryptococcal infections at other sites，the usual dose is 400 mg on the first day followed by 200-400mg once daily．Duration of the treatment for cryptococcal infections will depend on the clinical and mycological response，but is usually at least 6-8 weeks for cryptococcal meningitis．
For the prevention of relapse of cryptococcal meningitis in patients with AIDS，after the patient receives a full course of primary therapy．Fluconazole may be administered indefinitely at a daily dose of at least 100mg．
2．For candidemia，disseminated candidiasis and other invasive candidal infections，the usual dose is 400mg on the first day followed by 200mg daily．Depending on the clinical response，the dose may be increased to 400mg daily．Duration of treatment is based upon the clinical response．
3．For oropharyngeal candidiasis the usual dose is 50 mg once daily for 7-14 days．If necessary，treatment can be continued for longer periods in patients with severely compromised immune function．For atrophic oral candidiasis associate with dentures，the usual dose is 50mg once daily for 14 days administered concurrently with local antiseptic measures to the denture．
For other candidal infections of mucosa(except vaginal candidiasis，see below)，e．g．esophagitis，non-invasive bronchopulmonary infections，candiduria，mucocutaneous candidiasis，etc．，the usual effective dose is 50mg daily，given for 14-30 days．
In unusually difficult cases of mucosal candidal infections the dose may be increased to 100mg daily．
4．For vaginal candidiasis，fluconazole 150mg should be administered as a single oral dose．
5．For the prevention of fungal infections in patients with malignancy，the dose should be 50mg once daily while the patient is at risk as a consequence of receiving cytotoxic chemotherapy or radiotherapy．
6．For tinea pedis，tinea corporis，tinea cruris，tinea versicolor and dermal candidal infections the recommended dosage is 50mg once daily．Duration of treatment is normally 2 to 4 weeks but tinea pedis may require treatment for up to 6 weeks．Duration of treatment should not exceed 6 weeks．
·In Children
As stated in the Precautions section，use in children below the age of 16 is not recommended．However，when the treating physician considers fluconazole therapy imperative，the following daily doses for children age＞1 year with normal renal function are recommended：1-2 mg／kg for superficial candidal infections and 3-6 mg／kg for systemic candidal／cryptococcal in fections．
For children with impaired renal function the daily dose should be reduce in accordance with the guidelines given for adults，dependent on the degree of renal impairment．
·Use in elderly
Where there is no evidence of renal impairment，normal dosage recommendations should be adopted．For patients with renal impairment(creatinine clearance＜40ml／min)the dosage schedule should be adjusted as described below．
·Patients with renal impairment
Fluconazole is predominantly excreted in the urine as unchanged drug．No adjustments in single-dose therapy are necessary．In multiple-dose treatment of patients with renal impairment，normal doses should be given on days 1 and 2 or treatment and thereafter the dosage intervals or the daily dose should be modified in accordance with creatinine clearances as follows：
Creatinine Clearance Dosage Intervals／Daily Dose
(ml／min)
＞40 24 hours(normal dosage regimen)
21-40 48 hours or half normal daily dose
10-20 72 hours or one-third normal daily dose
Patients receiving regular One dose after every dialysis session
dialysis
Overdosage
In the event of overdosage，symptomatic treatment(with supportive measures and gastric lavage if necessary)may be adequate．Fluconazole is largely excreted in the urine；forced volume diuresis would probably increase the elimination rate．A three-hour hemodialysis session decreases plasma levels by approximately 50%．
DIFLUCAN*is a trademark of pfizer Inc．
Manufacturer
Pfizer Inc．NEW York，N．Y．，U．S．A．