Fidaxomicin

Fidaxomicin tablets are a macrolide antibacterial indicated in adult patients for the treatment of C. difficile -associated diarrhea. To reduce the development of drug-resistant bacteria and maintain the effectiveness of fidaxomicin tablets and other antibacterial drugs, fidaxomicin tablets should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile.

1.1Clostridioides

difficile -Associated Diarrhea Fidaxomicin tablets are indicated in adult patients for the treatment of C. difficile-associated diarrhea (CDAD).

1.2Usage To

reduce the development of drug-resistant bacteria and maintain the effectiveness of fidaxomicin tablets and other antibacterial drugs, fidaxomicin tablets should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Pediatric use information is approved for Cubist Pharmaceuticals LLC's DIFICID ® (fidaxomicin) tablets. However, due to Cubist Pharmaceuticals LLC's marketing exclusivity rights, this drug product is not labeled with that information.

Fidaxomicin tablets are administered orally with or without food. Adults One 200 mg tablet orally twice daily for 10 days.

2.1Important Administration Instructions Fidaxomicin

tablets are available for oral administration as 200 mg tablets. Fidaxomicin tablets are administered orally with or without food.

2.2Adult Patients The

recommended dosage for adults is one 200 mg fidaxomicin tablet orally twice daily for 10 days. Pediatric use information is approved for Cubist Pharmaceuticals LLC's DIFICID ® (fidaxomicin) tablets. However, due to Cubist Pharmaceuticals LLC's marketing exclusivity rights, this drug product is not labeled with that information.

Acute hypersensitivity reactions (angioedema, dyspnea, pruritus, and rash) have been reported. If a severe hypersensitivity reaction occurs, discontinue fidaxomicin tablets. Fidaxomicin tablets is not expected to be effective for the treatment of other types of infections due to minimal systemic absorption of fidaxomicin. Fidaxomicin tablets should only be used for the treatment of C. difficile -associated diarrhea. Development of drug-resistant bacteria: Only use fidaxomicin tablets for infection proven or strongly suspected to be caused by C. difficile.

5.1Hypersensitivity Reactions Acute

hypersensitivity reactions, including dyspnea, rash, pruritus, and angioedema of the mouth, throat, and face have been reported with fidaxomicin tablets. If a severe hypersensitivity reaction occurs, fidaxomicin tablets should be discontinued and appropriate therapy should be instituted. Some patients with hypersensitivity reactions to fidaxomicin tablets also reported a history of allergy to other macrolides.

Physicians prescribing fidaxomicin tablets to patients with a known macrolide allergy should be aware of the possibility of hypersensitivity reactions.

5.2Not for Use in Infections Other

than C. difficile -Associated Diarrhea Fidaxomicin tablets are not expected to be effective for the treatment of other types of infections due to minimal systemic absorption of fidaxomicin . Fidaxomicin tablets have not been studied for the treatment of infections other than CDAD. Fidaxomicin tablets should only be used for the treatment of CDAD.

5.3Development of Drug-Resistant Bacteria Prescribing

fidaxomicin tablets in the absence of 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.

Fidaxomicin tablets are contraindicated in patients who have known hypersensitivity to fidaxomicin or any other ingredient in fidaxomicin tablets . Fidaxomicin tablets are contraindicated in patients who have known hypersensitivity to fidaxomicin or any other ingredient in fidaxomicin tablets.

8.1Pregnancy Risk Summary The

limited available data on use of fidaxomicin tablets in pregnant women are insufficient to inform any drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. Embryo-fetal reproduction studies in rats and rabbits dosed intravenously during organogenesis revealed no evidence of harm to the fetus at fidaxomicin and OP-1118 (its main metabolite) exposures 65-fold or higher than the clinical exposure at the fidaxomicin tablets recommended dose . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In pregnant rats, fidaxomicin was administered intravenously at doses of 4, 8, and 15 mg/kg/day from gestation day 6 through 17 (during the period of organogenesis). No embryo/fetal effects were noted in this study at exposures (AUC) 193-fold higher for fidaxomicin, and 65-fold higher for OP-1118 than the clinical exposure at the fidaxomicin tablets recommended dose.

In pregnant rabbits, fidaxomicin was administered intravenously at doses of 2, 4, and 7.5 mg/kg/day from gestation day 6 through 18 (during the period of organogenesis). No embryo/fetal effects were noted in this study at exposures 66-fold higher for fidaxomicin, and 245-fold higher for OP-1118 than the clinical exposure at the fidaxomicin tablets recommended dose.

The most common adverse reactions in adults (incidence ≥2%) are nausea, vomiting, abdominal pain, gastrointestinal hemorrhage, anemia, and neutropenia. To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp., at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because

clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults The safety of fidaxomicin 200 mg tablets taken twice a day for 10 days was evaluated in 564 adult patients with CDAD in two active-controlled trials with 86.7% of patients receiving a full course of treatment. Thirty-three adult patients receiving fidaxomicin tablets (5.9%) withdrew from trials as a result of adverse reactions (AR).

The types of AR resulting in withdrawal from the study varied considerably. Vomiting was the primary adverse reaction leading to discontinuation of dosing; this occurred at an incidence of 0.5% in both the fidaxomicin tablets and vancomycin patients in Phase 3 trials. The most common selected adverse reactions occurring in ≥2% of adult patients treated with fidaxomicin tablets are listed in Table 2.

Table 2: Selected Adverse Reactions with an Incidence of ≥2% Reported in Fidaxomicin-Treated Adult Patients in Controlled Trials System Organ Class Adverse Reaction Fidaxomicin (N=564) Vancomycin (N=583) n (%) n (%) Blood and Lymphatic System Disorders Anemia 14 (2%) 12 (2%) Neutropenia 14 (2%) 6 (1%) Gastrointestinal Disorders Nausea 62 (11%) 66 (11%) Vomiting 41 (7%) 37 (6%) Abdominal Pain 33 (6%) 23 (4%) Gastrointestinal Hemorrhage 20 (4%) 12 (2%) The following adverse reactions were reported in <2% of adult patients taking fidaxomicin tablets in controlled trials: Gastrointestinal Disorders: abdominal distension, abdominal tenderness, dyspepsia, dysphagia, flatulence, intestinal obstruction, megacolon Investigations: increased blood alkaline phosphatase, decreased blood bicarbonate, increased hepatic enzymes, decreased platelet count Metabolism and Nutrition Disorders: hyperglycemia, metabolic acidosis Skin and Subcutaneous Tissue Disorders: drug eruption, pruritus, rash

6.2Post Marketing Experience The

following adverse reactions have been identified during post-approval use of fidaxomicin tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity reactions (dyspnea, angioedema, rash, pruritus) Pediatric use information is approved for Cubist Pharmaceuticals LLC's DIFICID ® (fidaxomicin) tablets.

However, due to Cubist Pharmaceuticals LLC's marketing exclusivity rights, this drug product is not labeled with that information.