General Information

Dificid (fidaxomicin) is a narrow-spectrum macrocyclic antibiotic.

Dificid is specifically indicated in adults for treatment of Clostridium difficile-associated diarrhea. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Dificid, it should be used only to treat infections that are proven or strongly suspected to be caused by Clostridium difficile. Dificid is also approved for the treatment of Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD) in children aged six months and older.

Dificid is supplied as a tablet designed for oral administration. The recommended dose is one 200 mg tablet orally twice daily for 10 days with or without food.

The recommended dose for pediatric patients weighing at least 12.5 kg and able to swallow tablets is one 200 mg Dificid tablet administered orally twice daily for 10 days. If unable to swallow tablets, pediatric patients may be dosed with Dificid oral suspension based on weight. Dificid oral suspension should be administered orally twice daily for 10 days.

Clinical Results

FDA Approval
The FDA approval of Dificid was based on two randomized, double-blinded, non-inferiority trials. The trials were designed to demonstrate the efficacy of Dificid (200 mg twice daily for 10 days) compared to vancomycin (125 mg four times daily for 10 days) in adults with Clostridium difficile-associated diarrhea (CDAD). The primary efficacy endpoints were the clinical response rate at the end of therapy, based upon improvement in diarrhea or other associated symptoms, and sustained clinical response 25 days after the end of treatment. Both endpoints were reached in both trials, showing that Dificid is non-inferior to vancomycin. The clinical response rate for both trials was 88% in the Dificid arms and 86% and 87% in the vancomycin arms. The sustained clinical response was 70% and 72% in the Dificid arms and 57% in the vancomycin arms.

The FDA’s approval of Dificid in pediatrics was based on a Phase 3, multicenter, investigator-blind, randomized, parallel group study (known as the SUNSHINE study), in which the safety and efficacy of fidaxomicin was evaluated in pediatric patients from 6 months to less than 18 years of age (one patient was less than six months of age). This study, sponsored by Astellas Pharma Europe B.V. (with Merck & Co., Inc. as collaborator) included 148 randomized patients aged <18 years with confirmed CDI, of whom 142 received either fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, four times daily) in a 2:1 ratio. Patients were randomized by age group, as follows: 30 patients from 6 months to <2 years; 49 patients age 2 to <6 years, 40 patients age 6 to <12 years and 29 patients age 12 to <18 years. CDAD clinical response in the overall pediatric population, assessed through two days following 10 days of treatment, was similar between the fidaxomicin and vancomycin groups (77.6% vs. 70.5%). Sustained clinical response, defined as the proportion of treated patients with confirmed clinical response and no CDAD recurrence through 30 days after the end of treatment, was higher for fidaxomicin than for vancomycin (68.4% vs. 50.0%).

Literature References

Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, Gorbach S, Sears P, Shue YK; OPT-80-003 Clinical Study Group Fidaxomicin versus vancomycin for Clostridium difficile infection The New England Journal of Medicine 2011 Feb 3;364(5):422-31

Tannock GW, Munro K, Taylor C, Lawley B, Young W, Byrne B, Emery J, Louie T A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin. Microbiology 2010 Nov;156(Pt 11):3354-9. Epub 2010 Aug 19