Is Fidaxomycin (Fidaxomicin) available for Clostridioides difficile treatment?

Fidaxomicin Availability and Use for Clostridioides difficile Infection

Fidaxomicin is FDA-approved and commercially available for the treatment of Clostridioides difficile infection (CDI) in adults, administered as 200 mg orally twice daily for 10 days. 1

Regulatory Status and Formulation

• Fidaxomicin received initial U.S. FDA approval in 2011 and is available as 200 mg film-coated tablets for oral administration with or without food 1
• The drug is indicated specifically for adult patients with C. difficile-associated diarrhea 1
• Safety and effectiveness have not been established in pediatric patients younger than 6 months of age 1

Current Guideline Recommendations

First-Line Treatment Positioning

The most recent 2021 IDSA/SHEA guidelines suggest using fidaxomicin rather than a standard course of vancomycin for initial CDI episodes (conditional recommendation, moderate certainty of evidence), though vancomycin remains an acceptable alternative 2

• Fidaxomicin demonstrates similar clinical cure rates to vancomycin (88% vs 85.5%) but significantly lower recurrence rates 2
• The 2019 WSES guidelines recommend fidaxomicin for severe CDI, especially in patients at higher risk for recurrence such as elderly patients or those receiving concomitant antibiotics 2

Recurrent CDI Treatment

For recurrent CDI episodes, the 2021 IDSA/SHEA guidelines suggest fidaxomicin (standard or extended-pulsed regimen) rather than standard vancomycin (conditional recommendation, low certainty evidence) 2

• Extended-pulsed fidaxomicin achieved 70% sustained clinical cure at 30 days compared to 59% with vancomycin (difference 11%, p=0.030) 2
• Fidaxomicin is particularly valuable for patients with multiple recurrences or those receiving concomitant antibiotics for other infections 2, 3

Clinical Efficacy Data

Non-Inferiority to Vancomycin

Multiple randomized controlled trials demonstrate fidaxomicin's non-inferior clinical cure rates:

• Clinical cure rates: 88.2% with fidaxomicin vs 85.8% with vancomycin in modified intention-to-treat analysis 2
• Recurrence rates significantly lower with fidaxomicin: 15.4% vs 25.3% with vancomycin (p=0.005) 2

Special Populations

• Patients receiving concomitant antibiotics had higher cure rates with fidaxomicin (90.2%) than vancomycin (73.3%, p=0.031) 2
• Fidaxomicin resulted in lower VRE acquisition (7%) compared to vancomycin (31%, p<0.001), an important consideration in settings with high VRE prevalence 2

Important Geographic and Clinical Considerations

Regional Variations

The Taiwan guidelines (2020) give fidaxomicin only a weak recommendation for first episodes of CDI, noting that fidaxomicin failed to show non-inferior efficacy specifically in Asian patients and that recurrence rates in Taiwan are lower than in Western countries 2

• Taiwan guidelines suggest fidaxomicin is best prescribed to patients with high risk of recurrence rather than as routine first-line therapy 2
• This represents a notable divergence from Western guidelines and highlights the importance of considering regional epidemiology

Cost Considerations

The average wholesale price is $4,871 per 20-tablet package (10-day course), which has remained stable since 2011 2

• Cost may be prohibitive without adequate insurance coverage, though patient-assistance mechanisms are available 2
• The 2021 IDSA/SHEA guidelines acknowledge that implementation depends upon available resources 2

Pharmacologic Advantages

• Fidaxomicin has minimal systemic absorption with fecal concentrations directly proportional to administered dose 1, 4
• The drug demonstrates bactericidal activity against C. difficile with a post-antibiotic effect of 6-10 hours 1
• Minimal activity against Bacteroides species helps maintain colonization resistance and protect against C. difficile recolonization 4

Critical Limitations and Contraindications

• Fidaxomicin is contraindicated in patients with known hypersensitivity to fidaxomicin or any tablet ingredient 1
• Acute hypersensitivity reactions (angioedema, dyspnea, pruritus, rash) have been reported; discontinue if severe reaction occurs 1
• No data exist on fidaxomicin efficacy in fulminant or life-threatening CDI; patients with hypotension, shock, ileus, or toxic megacolon were excluded from clinical trials 2
• Fidaxomicin is not expected to be effective for other infections due to minimal systemic absorption 1

Drug Interactions

No dose adjustment is warranted when fidaxomicin is coadministered with substrates of P-glycoprotein or CYP enzymes 1

• Cyclosporine (P-gp inhibitor) increases fidaxomicin exposure 1.92-fold and its metabolite OP-1118 by 4.11-fold, but no dose adjustment is recommended 1
• Fidaxomicin had no significant impact on pharmacokinetics of digoxin, midazolam, warfarin, or omeprazole 1

Practical Implementation

When fidaxomicin is selected, administer 200 mg orally twice daily for 10 days 1

• No dose adjustment needed for renal impairment 1
• Impact of hepatic impairment has not been evaluated, but significant effect is not expected since fidaxomicin undergoes minimal hepatic metabolism 1
• Most common adverse reactions (≥2% incidence) include nausea, vomiting, abdominal pain, gastrointestinal hemorrhage, anemia, and neutropenia 1