Your Health, We Care
Another NameDIFICLIR、ダフクリア、非达霉素
IndicationsDiarrhea
Reg No.04 L 1089/24
Inspection NO.0659-24
Fidaxomicin is an antimicrobial drug used to treat associated diarrhea caused by Clostridium difficile (CDAD), with significant therapeutic effect and targeting. It was approved by the FDA for marketing in the United States on May 27, 2011, and should be used only for the treatment of infections that have been proven or strongly suspected to be caused by Clostridium difficile.
Fidaxomicin, as an antimicrobial drug, has significant antimicrobial activity against Clostridium difficile and may reduce the recurrence rate, and its use should be strictly followed by the doctor's recommendations to avoid unnecessary drug use and the development of drug-resistant bacteria.
fidaxomicin
Fidaxomicin is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficileassociated diarrhea (CDAD).
The limited available data on use of Fidaxomicin in pregnant women are insufficient to inform any drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. Embryo-fetal reproduction studies in rats and rabbits dosed intravenously during organogenesis revealed no evidence of harm to the fetus at fidaxomicin and OP-1118 (its main metabolite) exposures 65-fold or higher than the clinical exposure at the Fidaxomicin recommended dose.
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
There is no information on the presence of fidaxomicin or its main metabolite, OP-1118, in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Fidaxomicin and any potential adverse effects on the breastfed infant from Fidaxomicin or from the underlying maternal condition.
The safety and effectiveness of Fidaxomicin for the treatment of CDAD have been established in pediatric patients 6 months to less than 18 years of age. Use of Fidaxomicin in these age groups is supported by evidence from adequate and well-controlled trials of Fidaxomicin in adults with CDAD and pharmacokinetic, safety and efficacy data from pediatric trials [see Clinical Pharmacology (12.3), Clinical Studies (14.2)]. No new safety signals associated with the use of Fidaxomicin in pediatric patients were identified in the pediatric trials
The safety and effectiveness of Fidaxomicin have not been established in pediatric patients younger than 6 months of age.
Of the total number of patients in controlled trials of Fidaxomicin, 50% were 65 years of age and over, while 31% were 75 and over. No overall differences in safety or effectiveness of Fidaxomicin compared to vancomycin were observed between these subjects and younger subjects. In controlled trials, elderly patients (≥65 years of age) had higher plasma concentrations of fidaxomicin and its main metabolite, OP-1118, versus non-elderly patients (<65 years of age) [see Clinical Pharmacology (12.3)]. However, greater exposures in elderly patients were not considered to be clinically significant. No dose adjustment is recommended for elderly patients.
No cases of acute overdose have been reported in humans. No drug-related adverse effects were seen in dogs dosed with fidaxomicin tablets at 9600 mg/day (over 100 times the human dose, scaled by weight) for 3 months.
Store Fidaxomicin tablets at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F). See USP controlled room temperature. Store in the original bottle.
The pharmacokinetic parameters of fidaxomicin and its main metabolite OP-1118 following a single dose of 200 mg in healthy adult males (N=14) are summarized in Table 4.
Fidaxomicin has minimal systemic absorption following oral administration, with plasma concentrations of fidaxomicin and OP-1118 in the ng/mL range at the therapeutic dose. In fidaxomicin-treated patients from controlled trials, plasma concentrations of fidaxomicin and OP-1118 obtained within the Tmax window (1-5 hours) were approximately 2- to 6-fold higher than Cmax values in healthy adults. Following administration of Fidaxomicin 200 mg twice daily for 10 days, OP-1118 plasma concentrations within the Tmax window were approximately 50%-80% higher than on Day 1, while concentrations of fidaxomicin were similar on Days 1 and 10.
In a food-effect study involving administration of Fidaxomicin to healthy adults (N=28) with a high-fat meal versus under fasting conditions, Cmax of fidaxomicin and OP-1118 decreased by 21.5% and 33.4%, respectively, while AUC0-t remained unchanged. This decrease in Cmax is not considered clinically significant, and thus, Fidaxomicin may be administered with or without food.
Fidaxomicin is mainly confined to the gastrointestinal tract following oral administration. In selected patients (N=8) treated with Fidaxomicin 200 mg twice daily for 10 days from controlled trials, fecal concentrations of fidaxomicin and OP-1118 obtained within 24 hours of the last dose ranged from 639-2710 µg /g and 213-1210 µg /g, respectively. In contrast, plasma concentrations of fidaxomicin and OP-1118 within the Tmax window (1-5 hours) ranged 2-179 ng/mL and 10-829 ng/mL, respectively.
Fidaxomicin is primarily transformed by hydrolysis at the isobutyryl ester to form its main and microbiologically active metabolite, OP-1118. Metabolism of fidaxomicin and formation of OP-1118 are not dependent on cytochrome P450 (CYP) enzymes. At the therapeutic dose, OP-1118 was the predominant circulating compound in healthy adults, followed by fidaxomicin.
Fidaxomicin is mainly excreted in feces. In one trial of healthy adults (N=11), more than 92% of the dose was recovered in the stool as fidaxomicin and OP-1118 following single doses of 200 mg and 300 mg. In another trial of healthy adults (N=6), 0.59% of the dose was recovered in urine as OP-1118 only following a single dose of 200 mg.
FDA,2020.05
