Side Effects of Dificid (fidaxomicin)

Dificid (fidaxomicin) is a macrolide antibiotic used in adults (18 years of age and older) to treat 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 Clostridium difficile.

Common side effects of Dificid include

• nausea,
• vomiting,
• abdominal pain,
• gastrointestinal bleeding,
• anemia, and
• low white blood cells (neutropenia).

Serious side effects of Dificid include

• fever,
• chills,
• body aches,
• flu symptoms,
• sores in the mouth and throat;
• pale skin,
• lightheadedness, or shortness of breath,
• rapid heart rate,
• trouble concentrating;
• black, bloody, or tarry stools; or
• coughing up blood or vomit that looks like coffee grounds.

There are no listed drug interactions of Dificid. 

There are no adequate and well-controlled studies of Dificid in pregnant women. Dificid should be used during pregnancy only if clearly needed. 

It is unknown if Dificid is excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when Dificid is administered to a breastfeeding woman.

• nausea (11%),
• vomiting (7%),
• abdominal pain (6%),
• gastrointestinal hemorrhage (4%),
• anemia (2%), and
• neutropenia (2%).

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of any other drug and may not reflect the rates observed in practice. The safety of Dificid 200 mg tablets taken twice a day for 10 days was evaluated in 564 patients with CDAD in two active-comparator controlled trials with 86.7% of patients receiving a full course of treatment.

Thirty-three patients receiving Dificid (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 and vancomycin patients in Phase 3 studies.

The following adverse reactions were reported in <2% of patients taking Dificid 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

Clinical 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.

The safety of Dificid 200 mg tablets taken twice a day for 10 days was evaluated in 564 patients with CDAD in two active-comparator controlled trials with 86.7% of patients receiving a full course of treatment.

Thirty-three patients receiving Dificid (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 and vancomycin patients in Phase 3 studies.

Table 1: Selected Adverse Reactions with an Incidence of ≥2% Reported in Dificid Patients in Controlled

The following adverse reactions were reported in <2% of patients taking Dificid 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

Post Marketing Experience

Adverse reactions reported in the post marketing setting arise from a population of unknown size and are voluntary in nature. As such, reliability in estimating their frequency or in establishing a causal relationship to drug exposure is not always possible.

Hypersensitivity reactions (dyspnea, angioedema, rash, and pruritus) have been reported.

• Fidaxomicin and its main metabolite, OP-1118, are substrates of the efflux transporter, P-glycoprotein (P-gp), which is expressed in the gastrointestinal tract.

Cyclosporine

• Cyclosporine is an inhibitor of multiple transporters, including P-gp. When cyclosporine was co-administered with Dificid, plasma concentrations of fidaxomicin and OP-1118 were significantly increased but remained in the ng/mL range.
• Concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) via P-gp inhibition; however, concomitant P-gp inhibitor use had no attributable effect on safety or treatment outcome of fidaxomicin-treated patients in controlled clinical trials.
• Based on these results, fidaxomicin may be co-administered with P-gp inhibitors and no dose adjustment is recommended.