1、轻度腹泻，肝酶的实验室测试水平轻微上升，以及头痛。一些病人经历了与输液相关的反应，其中多数为轻度。在具有重大的潜在医学状况的且正伴服多重药物的少数病人中，有严重肝异常的报道。Eraxis由纽约州的Pfizer公司生产。ERAXIS - anidulafungininjection, powder, lyophilized, for solutionRoerigERAXIS （anidulafungin） FOR INJECTIONINTRAVENOUS INFUSION, DILUTED WITH STERILE WATER FOR INJECTION （not for IV Bolus In
2、jection）DESCRIPTIONERAXIS for Injection is a sterile, lyophilized product for intravenous （IV） infusion that contains anidulafungin. ERAXIS （anidulafungin） is a semi-synthetic lipopeptide synthesized from a fermentation product ofAspergillusnidulans. Anidulafungin is an echinocandin, a class of anti
3、fungal drugs that inhibits the synthesis of 1,3-D-glucan, an essential component of fungal cell walls.ERAXIS （anidulafungin） is 1-（4R,5R）-4,5-dihydroxy-N2-4-（pentyloxy）1,1:4,1-terphenyl-4-ylcarbonyl-L-ornithineechinocandin B.Anidulafungin is a white to off-white powder that is practically insoluble
4、in water and slightly soluble in ethanol. In addition to the active ingredient, anidulafungin, ERAXIS for Injection contains the following inactive ingredients:50 mg/vial- fructose （50 mg）, mannitol （250 mg）, polysorbate 80 （125 mg）, tartaric acid （5.6 mg）, and sodium hydroxide and/or hydrochloric a
5、cid for pH adjustment.100 mg/vial- fructose （100 mg）, mannitol （500 mg）, polysorbate 80 （250 mg）, tartaric acid （11.2 mg）, and sodium hydroxide and/or hydrochloric acid for pH adjustment.The empirical formula of anidulafungin is C58H73N7O17and the formula weight is 1140.3.The structural formula is:P
6、rior to administration, ERAXIS for Injection requires reconstitution with sterile Water for Injection and subsequent dilution with either 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP （normal saline）.DO NOT dilute with other solutions or co-infuse with other medications or electr
7、olytes （seeDOSAGE AND ADMINISTRATION）.CLINICAL PHARMACOLOGYPharmacokineticsThe pharmacokinetics of anidulafungin following IV administration have been characterized in healthy subjects, special populations and patients. Systemic exposures of anidulafungin are dose-proportional and have low intersubj
8、ect variability （coefficient of variation 99%） to human plasma proteins.MetabolismHepatic metabolism of anidulafungin has not been observed. Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 （CYP450） isoenzymes. It is unlikely that anidulafungin will have
9、 clinically relevant effects on the metabolism of drugs metabolized by CYP450 isoenzymes.Anidulafungin undergoes slow chemical degradation at physiologic temperature and pH to a ring-opened peptide that lacks antifungal activity. Thein vitrodegradation half-life of anidulafungin under physiologic co
10、nditions is about 24 hours.In vivo, the ring-opened product is subsequently converted to peptidicdegradants and eliminated.ExcretionIn a single-dose clinical study, radiolabeled （14C） anidulafungin was administered to healthy subjects. Approximately 30% of the administered radioactive dose was elimi
11、nated in the feces over 9 days, of which less than 10% was intact drug. Less than 1% of the administered radioactive dose was excreted in the urine. Anidulafungin concentrations fell below the lower limits of quantitation 6 days post-dose. Negligible amounts of drug-derived radioactivity were recove
12、red in blood, urine, and feces 8 weeks post-dose.Special PopulationsPatients with fungal infectionsPopulation pharmacokinetic analyses from four Phase 2/3 clinical studies including 107 male and 118 female patients with fungal infections showed that the pharmacokinetic parameters of anidulafungin ar
13、e not affected by age, race, or the presence of concomitant medications which are known metabolic substrates, inhibitors or inducers.The pharmacokinetics of anidulafungin in patients with fungal infections are similar to those observed in healthy subjects. The pharmacokinetic parameters of anidulafu
14、ngin estimated using population pharmacokinetic modeling following IV administration of a maintenance dose of 50 mg/day or 100 mg/day （following a loading dose） are presented in Table 2.Table 2. Mean （%CV） Steady State Pharmacokinetic Parameters of Anidulafungin Following IV Administration of Anidul
15、afungin in Patients with Fungal Infections Estimated Using Population Pharmacokinetic Modeling100/50All the parameters were estimated by population modeling using a two-compartment model with first order elimination; AUCss, Cmax,ssand Cmin,ss（steady state trough plasma concentration） were estimated
16、using individual PK parameters and infusion rate of 1 mg/min to administer recommended doses of 50 and 100 mg/day. loading dose/daily maintenance doset1/2, is the predominant elimination half-life that characterizes the majority of the concentration-time profile.4.2 （22.4）7.2 （23.3）Cmin, ss1.6 （42.1
17、）3.3 （41.8）55.2 （32.5）110.3 （32.5）1.0 （33.5）26.5 （28.5）GenderDosage adjustments are not required based on gender. Plasma concentrations of anidulafungin in healthy men and women were similar. In multiple-dose patient studies, drug clearance was slightly faster （approximately 22%） in men.GeriatricDos
18、age adjustments are not required for geriatric patients. The population pharmacokinetic analysis showed that median clearance differed slightly between the elderly group （patients 65, median CL = 1.07 L/h） and the non-elderly group （patients 65, median CL = 1.22 L/h） and the range of clearance was s
19、imilar.RaceDosage adjustments are not required based on race. Anidulafungin pharmacokinetics were similar among Whites, Blacks, Asians, and Hispanics.HIV StatusDosage adjustments are not required based on HIV status, irrespective of concomitant anti-retroviral therapy.Hepatic InsufficiencyDosage adj
20、ustments are not required on the basis of mild, moderate or severe hepatic insufficiency. Anidulafungin is not hepatically metabolized. Anidulafungin pharmacokinetics were examined in subjects with Child-Pugh class A, B or C hepatic insufficiency. Anidulafungin concentrations were not increased in s
21、ubjects with any degree of hepatic insufficiency. Though a slight decrease in AUC was observed in patients with Child-Pugh C hepatic insufficiency, it was within the range of population estimates noted for healthy subjects.Renal InsufficiencyDosage adjustments are not required for patients with any
22、degree of renal insufficiency including those on hemodialysis. Anidulafungin has negligible renal clearance. In a clinical study of subjects with mild, moderate, severe or end stage （dialysis-dependent） renal insufficiency, anidulafungin pharmacokinetics were similar to those observed in subjects wi
23、th normal renal function. Anidulafungin is not dialyzable and may be administered without regard to the timing of hemodialysis.PediatricThe pharmacokinetics of anidulafungin after daily doses were investigated in immunocompromised pediatric （2 through 11 years） and adolescent （12 through 17 years） p
24、atients with neutropenia. The steady state was achieved on the first day after administration of the loading dose （twice the maintenance dose）, and the Cmaxand AUCssincreased in a dose-proportional manner. Concentrations and exposures following administration of maintenance doses of 0.75 and 1.5 mg/
25、kg/day in this population were similar to those observed in adults following maintenance doses of 50 and 100 mg/day, respectively （as shown in Table 3） （seePRECAUTIONS, Pediatric Use）.Table 3. Mean （%CV） Steady State Pharmacokinetic Parameters of Anidulafungin Following IV Administration of Anidulafungin Once Daily in Pediatric SubjectsPK ParameterAnidulafungin IV Dosing Regimen（LD/MD, mg/kg）1.5/0.753.0/1.5Data were collected on Day 5 loading dose/daily maintenan
