dizziness, headache, dysgeusia

Gastrointestinal disorders

vomiting, nausea, constipation

abdominal distention, flatulence, dry mouth 

Hepatobiliary disorders

alanine aminotransferase increased 

Description of selected adverse reactions 

Acute hypersensitivity reactions, such as angioedema and dyspnea, have been reported during post-marketing (see section 4.3 and 4.4). 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

No adverse reactions for acute overdose have been reported during clinical studies or from post-marketing data. However, the potential for adverse reactions cannot be ruled out and general supportive measures are recommended.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antidiarrheals, intestinal antiinflammatory/antiinfective agents, antibiotics, ATC code: A07AA12

Mechanism of action 

Fidaxomicin is an antibiotic belonging to the macrocyclic class of antibacterials.

Fidaxomicin is bactericidal and inhibits RNA synthesis by bacterial RNA polymerase. It interferes with RNA polymerase at a distinct site from that of rifamycins. Inhibition of the Clostridial RNA polymerase occurs at a concentration 20-fold lower than that for the E. coli enzyme (1 μM vs. 20 μM), partly explaining the significant specificity of fidaxomicin activity. Fidaxomicin has been shown to inhibit C. difficile sporulation in vitro. 

Pharmacokinetic/Pharmacodynamic (PK/PD) relationship 

Fidaxomicin is a locally acting drug. As a topical agent, systemic PK/PD relationships cannot be established, however in vitro data show fidaxomicin to have time-dependent bactericidal activity and suggest time over MIC may be the parameter most predicative of clinical efficacy.

Breakpoints 

Fidaxomicin is a topically acting drug that cannot be used to treat systemic infections; therefore the establishment of a clinical breakpoint is not relevant. The epidemiological cut-off value for fidaxomicin and C. difficile, distinguishing the wild-type population from isolates with acquired resistance traits, is ≥1.0 mg/L.

Antimicrobial spectrum 

Fidaxomicin is a narrow spectrum antimicrobial drug with bactericidal activity against C. difficile. Fidaxomicin has an MIC90 of 0.25 mg/L versus C. difficile, and its main metabolite, OP-1118, has an MIC90 of 8 mg/L. Gram negative organisms are intrinsically not susceptible to fidaxomicin. 

Effect on the intestinal flora 

Studies have demonstrated that fidaxomicin treatment did not affect Bacteroides concentrations or other major components of the microbiota in the faeces of CDI patients. 

Mechanism of resistance