DIFICID®

(fidaxomicin) tablets, for oral use

Efficacy

Study design and clinical end points

DIFICID was studied vs vancomycin in two phase 3 Clostridium difficile–associated diarrhea (CDAD) trials.

Study design

  • Two randomized, double-blind, noninferiority trials

Patients

  • 1,105 patients ≥18 years of age
  • Diagnosis of C. difficile–associated diarrhea as defined by:
    • >3 unformed bowel movements (UBM) (or >200 mL of unformed stool for subjects having rectal collection devices) in the 24 hours before randomization
    • Presence of C. difficile toxin A or B in stool sample within 48 hours of randomization
  • No more than 24 hours of pretreatment with vancomycin or metronidazole
  • No more than one prior C. difficile–associated diarrhea episode in past 3 months
  • 37% of patients had severe C. difficile–associated diarrhea (defined as ≥10 UBM per day or WBC ≥15,000/mm3)
  • 16% of patients studied had a prior episode of CDAD within the last 3 months
  • 50% of patients were ≥65 years of age and 31% were ≥75 years of age
  • Exclusion criteria : Life-threatening/fulminant infection, hypotension, septic shock, peritoneal signs, significant dehydration, or toxic megacolon. 

Treatment Regimens for DIFICID® (fidaxomicin) 200mg BID for 10 Days vs Vancomycin 125mg QID for 10 Days

Clinical end points 

Primary end point: Clinical response rate at the end of 10-day treatment
  • Clinical response was defined as improvement in diarrhea or other symptoms, such that further C. difficile–associated diarrhea treatment was not needed.
Additional efficacy end point: Sustained response 25 days after the end of treatment
  • Sustained response was defined as clinical response at the end of treatment and survival without proven or suspected C. difficile–associated diarrhea recurrence through 25 days beyond the end of treatment.

Initial and Sustained Clinical End Points for DIFICID® (fidaxomicin) vs Vancomycin

Definitions

CDAD = Clostridium difficile–associated diarrhea 

UBM = unformed bowel movements 

WBC = white blood cell

Indication

DIFICID is a macrolide antibacterial drug indicated in adults (≥18 years of age) for treatment of Clostridium difficile–associated diarrhea (CDAD). 

To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by C difficile.

Selected Safety Information

  • DIFICID is contraindicated in patients with hypersensitivity to fidaxomicin.
  • DIFICID should not be used for systemic infections.
  • Acute hypersensitivity reactions, including dyspnea, rash pruritus, and angioedema of the mouth, throat, and face have been reported with fidaxomicin. If a severe hypersensitivity reaction occurs, DIFICID should be discontinued and appropriate therapy should be instituted.
  • Only use DIFICID for infection proven or strongly suspected to be caused by C difficile. Prescribing DIFICID in the absence of a proven or strongly suspected C difficile infection is unlikely to provide benefit to the patient and increases the risk of development of drug-resistant bacteria.
  • The most common adverse reactions reported in clinical trials are nausea (11%), vomiting (7%), abdominal pain (6%), gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%).
  • Among patients receiving DIFICID, 33 (5.9%) withdrew from trials as a result of adverse reactions. Vomiting was the primary adverse reaction leading to discontinuation of dosing (incidence of 0.5% for both DIFICID and vancomycin patients).
  • The safety and effectiveness of DIFICID in patients <18 years of age have not been established.
  • The recommended dose of DIFICID is one 200 mg tablet orally twice daily for 10 days, with or without food.
  • No dose adjustment is recommended for patients ≥65 years of age.
  • No dose adjustment is recommended for patients with renal impairment.
  • No dosage adjustments are recommended when co-administering fidaxomicin with substrates of P-gp or CYP enzymes.
  • The impact of hepatic impairment on the pharmacokinetics of fidaxomicin has not been evaluated; however, because fidaxomicin and its active metabolite (OP-1118) do not appear to undergo significant hepatic metabolism, elimination of fidaxomicin and OP-1118 is not expected to be significantly affected by hepatic impairment.
Before prescribing DIFICID® (fidaxomicin), please read the Prescribing Information.
AINF-1245964-000007/18