DIFICID

1 Dosing Considerations DIFICID® (fidaxomicin) tablets can be administered with or without food (see DRUG INTERACTIONS, Drug-Food Interactions). 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 susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. 2 Recommended Dose and Dosage Adjustment The recommended dose for adults ≥18 years of age is one 200-mg DIFICID® tablet orally twice daily for 10 days with or without food.

No dose adjustment in adults is necessary based on age or gender. No dose adjustment is recommended based on renal function or hepatic impairment.

PrDIFICID® (fidaxomicin) Page 5 of 24 Pediatrics <18 years of age:

The safety and efficacy of DIFICID® in patients below18 years of age have not been established.

Geriatrics ≥65 years of age:

No dose adjustment is recommended for elderly patients. 3 Administration The recommended dose for adults ≥18 years of age is one 200-mg DIFICID® tablet orally twice daily for 10 days with or without food. 4 Missed Dose If a dose is missed, it should be taken as soon as possible.

However, if it is almost time for the next dose, no additional dose should be taken and the regular dosing schedule should be resumed. No more than two doses of DIFICID® (1 tablet twice a day) should be taken in a 24-hour period.

6%. 2%). The majority of adverse drug reactions were reported as mild or moderate in severity. No serious adverse drug reaction considered to be related to DIFICID® by the investigator was reported by more than 1 subject. 9%) groups. The types of adverse events resulting in withdrawal from the study were varied.

5%. 8%) receiving DIFICID® during the Phase 3 trials experienced rash, pruritus, or rash-like symptoms. Reported symptoms were mild and self-limiting or resolved with anti-histamine treatment. Compared to the comparator, more patients treated with DIFICID® experienced neutropenia (2% versus 1%) and gastrointestinal hemorrhage (4% versus 2%).

However, these events were considered not drug-related by the investigators. The overall incidence of mild, moderate, and severe adverse events was similar for the DIFICID® and comparator groups. 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The safety of DIFICID® 200 mg tablets taken twice a day for 10 days was evaluated in 564 patients with C.

7% of patients receiving a full course of treatment. Adverse drug reactions (as judged by the investigator to be possibly or definitely related to DIFICID®) that occurred at a rate of ≥1% are shown in Table 2 and the Less Common Clinical Trial Adverse Drug Reactions are presented below the table.

3 Less Common Clinical Trial Adverse Reactions Gastrointestinal Disorders: abdominal distension, flatulence, dry mouth. Hepatobiliary Disorders: alanine aminotransferase increased. Metabolism and Nutrition Disorders: anorexia. Nervous System Disorders: dizziness, dysgeusia, headache.

General Not for Systemic Infections Since there is minimal systemic absorption of fidaxomicin, DIFICID® should not be used for the treatment of systemic infections. Development of Drug Resistant Bacteria 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 the development of drug-resistant bacteria. Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Film-coated tablet/ 200 mg/ fidaxomicin Tablets: Butylated Hydroxytoluene, Hydroxypropyl Cellulose, Magnesium Stearate, Microcrystalline Cellulose, Pregelatinised Starch, Sodium Starch Glycolate Coat: Lecithin (Soy), Polyethylene glycol Polyvinyl Alcohol, Talc, Titanium Dioxide.

PrDIFICID® (fidaxomicin) Page 6 of 24 Carcinogenesis and Mutagenesis Long-term carcinogenicity studies have not been conducted to evaluate the carcinogenic potential of fidaxomicin. Under the conditions tested, fidaxomicin was not mutagenic in the Ames assay and did not show a biologically significant increase in DNA damage in the rat micronucleus and comet assays.

However, fidaxomicin was clastogenic in Chinese hamster ovary cells (see NON-CLINICAL TOXICOLOGY). Cardiovascular Electrocardiogram (ECG) parameters and QT intervals (QTc) were measured in patients participating in Phase 3 studies. No clinically significant changes from baseline to end of therapy in mean ECG parameters were seen.

There was no evidence of QTc prolongation with DIFICID® treatment and there was no association between QTc prolongation and plasma levels of fidaxomicin or OP-1118, its main metabolite. In an in vitro electrophysiology study, fidaxomicin and its main metabolite, OP-1118, had no effect on the hERG channel.

Gastrointestinal Due to limited clinical data, DIFICID® should be used with caution in patients with pseudomembranous colitis, fulminant or life threatening CDI. Patients with more than one previous episode of CDI within the 3 months prior to initiation of treatment have not been studied.

Hypersensitivity to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.