Study design and clinical end points

DIFICID was studied in adults vs vancomycin in two phase 3 Clostridioides (formerly 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 white blood cell (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

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.

Clinical End Points for Phase 3 Trial of DIFICID® (fidaxomicin) vs Vancomycin

Indication

DIFICID® (fidaxomicin) is a macrolide antibacterial drug indicated in adult and pediatric patients 6 months of age and older for treatment of Clostridioides 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 who have known hypersensitivity to fidaxomicin or any other ingredient in DIFICID.
Acute hypersensitivity reactions, including dyspnea, rash, pruritus, and angioedema of the mouth, throat, and face have been reported with DIFICID. If a severe hypersensitivity reaction occurs, DIFICID should be discontinued and appropriate therapy should be instituted.
DIFICID is not expected to be effective for the treatment of other types of infections due to minimal systemic absorption of fidaxomicin. DIFICID has not been studied for the treatment of infections other than CDAD. DIFICID should only be used for the treatment of CDAD.
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 in adults reported in clinical trials are nausea (11%), vomiting (7%), abdominal pain (6%), gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%).
Among adult 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 most common adverse reactions in pediatric patients treated with DIFICID are pyrexia (13.3%), abdominal pain (8.2%), vomiting (7.1%), diarrhea (7.1%), constipation (5.1%), increased aminotransferases (5.1%), and rash (5.1%).
The safety and effectiveness of DIFICID in patients <6 months of age have not been established.
The recommended dose of DIFICID for adults and pediatric patients weighing at least 12.5 kg and able to swallow tablets is one 200 mg tablet orally twice daily for 10 days, with or without food. The recommended weight-based dosage of the oral suspension in pediatric patients (weighing at least 4 kg) is twice daily for 10 days.
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. The Patient information also is available.

Indication Indication

DIFICID® (fidaxomicin) is a macrolide antibacterial drug indicated in adult and pediatric patients 6 months of age and older for treatment of Clostridioides difficile-associated diarrhea (CDAD).

DIFICID® (fidaxomicin) is a macrolide antibacterial drug indicated in adult

DIFICID® (fidaxomicin) is a macrolide antibacterial drug indicated in adult and pediatric patients 6 months of age and older for treatment of Clostridioides difficile-associated diarrhea (CDAD)

Selected Safety Information Selected Safety Information

DIFICID is contraindicated in patients who have known hypersensitivity to fidaxomicin or any other ingredient in DIFICID.
Acute hypersensitivity reactions, including dyspnea, rash, pruritus, and angioedema of the mouth, throat, and face have been reported with DIFICID. If a severe hypersensitivity reaction occurs, DIFICID should be discontinued and appropriate therapy should be instituted.
DIFICID is not expected to be effective for the treatment of other types of infections due to minimal systemic absorption of fidaxomicin. DIFICID has not been studied for the treatment of infections other than CDAD. DIFICID should only be used for the treatment of CDAD.
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 in adults reported in clinical trials are nausea (11%), vomiting (7%), abdominal pain (6%), gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%).
Among adult 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 most common adverse reactions in pediatric patients treated with DIFICID are pyrexia (13.3%), abdominal pain (8.2%), vomiting (7.1%), diarrhea (7.1%), constipation (5.1%), increased aminotransferases (5.1%), and rash (5.1%).
The safety and effectiveness of DIFICID in patients <6 months of age have not been established.
The recommended dose of DIFICID for adults and pediatric patients weighing at least 12.5 kg and able to swallow tablets is one 200 mg tablet orally twice daily for 10 days, with or without food. The recommended weight-based dosage of the oral suspension in pediatric patients (weighing at least 4 kg) is twice daily for 10 days.
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.