In the combined phase III trial data, the most common adverse events in the fidaxomicin groups included nausea (11%), vomiting (7.3%), headache (6.6%), abdominal pain (5.9%), diarrhoea (5%) and constipation (4.4%). Hypersensitivity has been reported and is a contraindication to fidaxomicin use.
After oral administration, there is minimal systemic absorption of fidaxomicin. It is hydrolysed to the active metabolite, OP-1118, and most of the dose is excreted in the faeces. Co-administration with P-glycoprotein inhibitors such as cyclosporin, ketoconazole or verapamil may increase systemic fidaxomicin, however dose adjustments are not recommended. Inhibition of cytochrome P450 2C9 and 3A4/5 could potentially occur in the gastrointestinal tract and may affect the bioavailability of other drugs.
Due to lack of data, fidaxomicin should be used with caution in patients with hepatic or renal impairment. Fidaxomicin is a pregnancy category B1 drug with little data in humans. It is also not known if it is excreted in breast milk so caution is urged in pregnant and breastfeeding women.
Fidaxomicin appears to be a safe and effective alternative to vancomycin for diarrhoea caused by C. difficile. It is not yet known how it will compare to metronidazole which is recommended for mild to moderate disease managed in the community.1 There is limited evidence for fidaxomicin's use in severe infections as these patients were excluded from the trials. Repeated courses of fidaxomicin have not been studied, however recurrence was less common with fidaxomicin than with vancomycin. The safety and efficacy of fidaxomicin in children has not been established.