Dosing and uses of Dificid (fidaxomicin)
Adult dosage forms and strengths
tablet
- 200mg
Clostridium Difficile Colitis
Macrolide antibiotic indicated for Clostridium difficile-associated diarrhea in adults
200 mg PO q12hr for 10 days
May take with or without food
Renal Impairment
Dose adjustment not necessary
Hepatic Impairment
Not studied; dose adjustment not necessary since minimally absorbed
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Clostridium difficile Infection (Orphan)
Indicated for Clostridium difficile infection in pediatric patients 16 yr or younger
Orphan indication sponsor
- Optimer Pharmaceuticals, Inc; 10110 Sorrento Valley Road; San Diego, CA 92121
Dificid (fidaxomicin) adverse (side) effects
>10%
Nausea (11%)
1-10%
Vomiting (7%)
Abdominal pain (6%)
Gastrointestinal hemorrhage (4%)
Anemia (2%)
Neutropenia (2%)
<1%
Increased alkaline phosphatase
Decreased blood bicarbonate
Drug eruption
Increased hepatic enzymes
Megacolon
Warnings
Contraindications
Hypersensitivity
Cautions
Not indicated for systemic infections
Only use for infection proven or strongly suspected to be caused by C difficile to avoid development of drug resistant bacteria
Acute hypersensitivity reactions, including dyspnea, rash, pruritus, and angioedema of the mouth, throat, and face reported; discontinue and treat appropriately if reaction occurs therapy should be instituted
Some patients with hypersensitivity reactions also reported a history of allergy to other macrolides
Pregnancy and lactation
Pregnancy category: B
Lactation: Unknown whether distributed in breast milk; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dificid (fidaxomicin)
Mechanism of action
Macrolide antibiotic; bactericidal against C difficile in vitro, inhibiting RNA synthesis by RNA polymerases
Absorption
Bioavailability: Minimal systemic absorption
Peak Plasma Time: 2 hr (range 1-5 hr)
Peak Plasma Concentration: 5.2 ng/mL (+/- 2.81)
AUC: 14 ng•hr/mL
P-gp substrate, but not significantly affected by P-gp inhibitors
Distribution
Fecal Concentrations: 639-2710 mcg/g; OP-1118 213-1210 mcg/g
Metabolism
Metabolized by hydrolysis at the isobutyryl ester to form OP-1118
Metabolites: OP-1118 (active metabolite)
Enzyme substrate, inhibitor, or inducer: Not dependent on CYP450 enzymes
Elimination
Half-life: 9 hr
Excretion: Feces (92%)
