jority of the administered dose (over 92%) was recovered in the stool as fidaxomicin or its metabolite OP-1118 (66%). The main elimination pathways of systemically available fidaxomicin have not been characterized. Elimination through urine is negligible (<1%). Only very low levels of OP-1118 and no fidaxomicin was detectable in human urine. The half life of fidaxomicin is approximately 8-10 h.
Special populations
Elderly
Plasma levels appear to be elevated in the elderly (age ≥ 65 years). Fidaxomicin and OP-1118 levels were approximately 2 times higher in patients ≥ 65 years compared to patients < 65 years. This difference is not considered clinically relevant.
Inflammatory bowel disease
Data from an open label, single arm study in CDI patients with concomitant inflammatory bowel disease (IBD) indicated no major difference in plasma concentrations of fidaxomicin or its main metabolite OP-1118 in patients with IBD as compared with patients without IBD in other studies. The maximum fidaxomicin and OP-1118 plasma levels in CDI patients with concomitant IBD were within the range of levels found in CDI patients without IBD.
Hepatic impairment
Limited data from patients with an active history of chronic hepatic cirrhosis in the Phase 3 studies showed that median plasma levels of fidaxomicin and OP-1118 may be approximately 2- and 3-fold higher, respectively, than in non-cirrhotic patients.
Renal impairment
Limited data suggest that there is no major difference in plasma concentration of fidaxomicin or OP-1118 between patients with reduced renal function (creatinine clearance < 50 ml/min) and patients with normal renal function (creatinine clearance ≥ 50 ml/min).
Gender, weight and race
Limited data suggest that gender, weight and race do not have any major influence on the plasma concentration of fidaxomicin or OP-1118.
5.3 Preclinical safety data
Nonclinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeat dose toxicity, genotoxicity, and reproductive toxicity.
Reproductive and fertility parameters showed no statistically significant differences in rats treated with fidaxomicin at doses up to 6.3 mg/kg/day (intravenous).
6. Pharmaceutical particulars
6.1 List of excipients
Core tablets:
Microcrystalline cellulose
Pregelatinised starch (maize)
Hyroxypropyl cellulose
Butylated hydroxytoluene
Sodium starch glycolate
Magnesium stearate
Coating:
Polyvinyl alcohol
Titanium dioxide (E171)
Talc
Polyethylene glycol
Lecithin (soy)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
100 x 1 film-coated tablet in alu/alu perforated unit dose blisters.
20 x 1 film-coated tablet in alu/alu perforated unit dose blisters.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
