New Drug Update: Dificid® (fidaxomicin)

As seen in Consultant Connection August 2012 Issue
Taylor Gauthier, ONU, PharmD Candidate 2013, ICP Clinical Pharmacy Student

Dificid® is an oral antibiotic approved to treat C. difficile- associated diarrhea (CDAD) in adults. C. difficile infection is associated with approximately 14,000 deaths each year in the US with more than 90 percent of deaths in patients 65 years of age or greater. Dificid® is manufactured as a 200 mg tablet. It is a poorly absorbed macrolide antibiotic that works locally in the GI tract to fi ght C. difficile. The recommended dose for treatment of CDAD is 200 mg twice a day for 10 days. The most common side effects are nausea, vomiting, and abdominal pain.

Place in Therapy

The Infectious Disease Society of America (IDSA) guidelines for the treatment of C. difficile infection were published prior to the approval of Dificid® and have not yet been updated to include its place in therapy.  The current guidelines recommend specifi c treatments based on the severity of the infection and whether the infection is a fi rst time infection or recurring infection. The  recommended drug for treatment of a mild or moderate infection is metronidazole. For a more severe infection, vancomycin is the drug of choice. The current guidelines are further defined in Table 1. Updated guidelines are expected to be released by the IDSA in the fall of 2013.

Table 1. IDSA Recommendations for the Treatment of C. diffi cile Infection in Adults

Type of Infection Defining Characteristics Recommended Treatment
Initial- mild or moderate WBC < 15,000 and SCr < 1.5 times baseline Metronidazole 500 mg by mouth TID x 10-14 days
Initial-severe WBC < 15,000 and SCr < 1.5 times baseline Vancomycin 125 mg by mouth QID x 10-14 days
Initial-complicated WBC > 15,000 or SCr > 1.5  times baseline WITH hypotension,
shock, ileus, megacolon
Vancomycin 500 mg QID by mouth or NG tube
+/- metronidazole 500 mg Q8H
1st Recurrence -- Same as initial episode based on type of infection
2nd Recurrence -- Tapered or pulsed vancomycin

Published clinical trials have shown Dificid® to be at least as effective as vancomycin for the treatment of CDAD. A study conducted by Louie and colleagues looked at the effectiveness of Difi cid® compared to vancomycin for the treatment of CDAD. Trial participants were given either a 10 day treatment regimen of oral Dificid® (200 mg twice daily) or oral vancomycin (125 mg four times a day). Dificid® was found to be as effective as vancomycin for the treatment of CDAD, and the recurrence of infection caused by certain strains of C. difficile was found to be lower with Dificid® treatment. When comparing costs, Dificid® is significantly more expensive than vancomycin. The cost of 10 days of therapy with Dificid® is close to $3000. More studies are needed to determine when the use of Dificid® will be the most benefi cial. Until this information is available, current treatment guidelines should be followed, and Dificid® will likely be reserved for patients
that have previously failed treatment with vancomycin.

References:
1.Centers for Disease Control and Prevention [homepage on the internet]. Atlanta (GA): Centers for Disease Control and Prevention; Life threatening germ poses threat across medical facilities. 2012. Accessed from: http://www.cdc.gov/media/releases/2012/p0306_cdiff.html
2. Dificid® (fi daxomicin)[product information]. San Diego, CA: Optimer Pharmaceuticals Inc, 2011.
3. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium diffi cile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431- 55.
4. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium diffi cile infection. N Engl J Med. 2011;364:422-31.
5. Song JC, Hsiao P, Tran S. Fidaxomicin: cost considerations for the treatment of Clostridium diffi cile infection. IDA on the edge: a critical clinical update, 2011.


Back to Articles