FIDAXOMICIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FIDAXOMICIN (FIDAXOMICIN).
Fidaxomicin is an RNA polymerase inhibitor that acts bactericidal against Clostridioides difficile by inhibiting transcription via binding to RNA polymerase, leading to cell death. It has minimal systemic absorption and narrow spectrum of activity.
| Metabolism | Minimally metabolized; primarily excreted unchanged in feces; small amount undergoes hydrolysis to its major metabolite, OP-1118, which has some antibacterial activity. No significant hepatic metabolism via CYP450 enzymes. |
| Excretion | Fidaxomicin is primarily eliminated via fecal excretion as unchanged drug (92%), with minimal renal excretion (<1%). Biliary elimination accounts for a minor fraction. |
| Half-life | Terminal elimination half-life is approximately 11.7 hours (range 8–20 hours) in patients with Clostridium difficile infection, supporting twice-daily dosing. |
| Protein binding | Approximately 86% bound to plasma proteins, predominantly albumin. |
| Volume of Distribution | Volume of distribution is approximately 9 L/kg (range 7–11 L/kg), indicating extensive tissue distribution beyond plasma. |
| Bioavailability | Oral bioavailability is extremely low (<0.5%) due to minimal systemic absorption; acts locally in the gastrointestinal tract. |
| Onset of Action | Clinical response typically observed within 24–48 hours of oral administration due to local action in the colon. |
| Duration of Action | Duration of action persists throughout the 10-day treatment course; sustained fecal concentrations above MIC for C. difficile up to 5 days after last dose. |
200 mg orally twice daily for 10 days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment, including dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for age ≥6 months: 200 mg orally twice daily for 10 days; for weight <12.5 kg: 160 mg (4 mL suspension) orally twice daily for 10 days. |
| Geriatric use | No dose adjustment required; clinical studies included elderly patients with no differences in safety or efficacy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FIDAXOMICIN (FIDAXOMICIN).
| Breastfeeding | No data on excretion in human milk; low systemic absorption suggests minimal transfer. M/P ratio unknown. Caution recommended; consider benefit of therapy and risk to infant. |
| Teratogenic Risk | Fidaxomicin has low systemic absorption; no human pregnancy data available. Animal studies show no teratogenicity at doses up to 20 times the human exposure based on AUC. Risk cannot be excluded, but due to limited systemic exposure, fetal risk is likely low. Use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to fidaxomicin or any component of the formulation."]
| Precautions | ["Not effective for systemic infections.","May cause hypersensitivity reactions including angioedema and rash.","Monitor for development of antibiotic-associated diarrhea due to other pathogens.","Use with caution in patients with severe hepatic impairment (not studied)."] |
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| No specific fetal monitoring required due to low systemic absorption. Standard prenatal care. |
| Fertility Effects | No adverse effects on fertility observed in animal studies at clinically relevant doses. |