Dificid (fidaxomicin)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Fidaxomicin is a macrolide antibiotic.
Fidaxomicin, a macrolide antibiotic, is a fermentation product obtained from the Actinomycete Dactylosporangium aurantiacum. Fidaxomicin inhibits bacterial RNA synthesis through binding to RNA polymerase. In vitro, fidaxomicin exhibits bactericidal activity against Clostridioides difficile (formerly known as Clostridium difficile) and demonstrates a prolonged post-antibiotic effect against C. difficile of approximately 6-10 hours.
Fidaxomicin has demonstrated activity against the majority of C. difficile isolates in both in vitro studies and clinical infections.
Cross-resistance between fidaxomicin and other anti-infectives has not been reported to date. In vitro data indicate a low frequency of spontaneous resistance development in C. difficile. A single mutation (Val-1143-Gly) in the beta subunit of RNA polymerase was identified in C. difficile obtained from a patient who had recurrence of CDAD after fidaxomicin treatment.
Although C. difficile isolated from this patient at baseline had a fidaxomicin MIC of 0.06 mcg/mL, the MIC was 16 mcg/mL at the time of recurrence.
Following oral administration of fidaxomicin, only minimal systemic absorption occurs and the drug remains mainly confined to and acts locally in the GI tract. Following administration of a single dose of fidaxomicin 200 mg in healthy adult males, the time to peak plasma concentrations is approximately 2 hours for the drug and 1.02 hours for its main metabolite (OP-1118). Although plasma concentrations of fidaxomicin and OP-1118 at 1-5 hours after a dose are approximately 2-6 times higher in patients with Clostridioides difficile infection than in healthy adults, plasma concentrations remain in the ng/mL range.
Administration with a high-fat meal decreases peak plasma concentrations of fidaxomicin and OP-1118 by approximately 22 and 33%, respectively, but AUC is not affected and the effect of food is not considered clinically important.
Fidaxomicin is mainly transformed by hydrolysis at the isobutyryl ester to form OP-1118, the main, microbiologically active metabolite. At the therapeutic dose, OP-1118 was the predominant circulating compound in healthy adults, followed by fidaxomicin. Metabolism of fidaxomicin and formation of OP-1118 are not dependent on cytochrome P-450 (CYP) isoenzymes.
Fidaxomicin is excreted principally in feces. More than 92% of an oral dose is recovered in feces as fidaxomicin and OP-1118; less than 1% of a dose is recovered in urine as OP-1118. The plasma elimination half-lives of fidaxomicin and OP-1118 in adults are approximately 9 and 10 hours, respectively.
Plasma concentrations of fidaxomicin and OP-1118 at 1-5 hours after a dose are approximately 2-4 times higher in geriatric patients >=65 years of age than in adults <65 years of age; this is not considered clinically important. Plasma levels of fidaxomicin and OP 1118 at 1-5 hours after dosing were comparable between male and female patients receiving 200 mg twice daily for 10 days, indicating no gender-related differences.
USES: This medication is used to treat a severe intestinal condition (C. difficile-associated diarrhea) due to a certain type of bacteria. This condition may rarely occur after taking antibiotics. Symptoms include diarrhea that doesn't stop, stomach/abdominal pain or cramping, and blood/mucus in your stool.
Fidaxomicin is known as a macrolide antibiotic. It works by stopping the growth of this bacteria. This antibiotic works in the intestines and is not absorbed by your body.
It should only be used to treat this type of intestinal bacterial infection. It will not work for other types of infections, including viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.
Generic name: fidaxomicin
Pronunciation: (fye-DAX-oh-MYE-sin)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Dificid
Indications
The following indications are listed for Dificid:
- Clostridioides Difficile Infection
Also known as: Antibiotic-Associated Colitis, Antibiotic-Induced Pseudomembranous Enterocolitis, C. Diff. Infection, C. Difficile Colitis, Clostridioides Difficile-Associated Diarrhea, Clostridium Difficile Infection, Clostridium Difficile-Associated Diarrhea, Clostridium Enterocolitis, Diarrhea Associated With Pseudomembranous Colitis, Pseudomembranous Colitis, Pseudomembranous Enteritis.
Dosing
No dosing information is available for this tab.
Fidaxomicin is administered orally without regard to food.
Fidaxomicin is commercially available as film-coated tablets containing 200 mg of the drug and as granules for oral suspension that yield a 40 mg/mL concentration upon reconstitution.
Pediatric patients may be dosed with fidaxomicin oral suspension if they are unable to swallow tablets.
Store fidaxomicin tablets and granules for oral suspension at 20-25degreesC (excursions permitted to 15-30degreesC).
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Fidaxomicin is a P-glycoprotein (P-gp) substrate, P-gp inhibitor, and inhibitor of major cytochrome P-450 (CYP) enzymes expressed in the GI tract (CYP3A4, CYP2C9, and CYP2C19). Metabolism of fidaxomicin and formation of OP-1118 are not dependent on CYP isoenzymes.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Hypersensitivity to fidaxomicin or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects (>=2%) reported in adults with oral fidaxomicin include GI effects such as nausea, vomiting, abdominal pain, and GI hemorrhage, as well as hematologic reactions including anemia and neutropenia.
Among pediatric patients treated with fidaxomicin, adverse effects occurring in >=5% of patients include pyrexia, abdominal pain, vomiting, diarrhea, constipation, increased aminotransferases, and rash.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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The safety and efficacy of fidaxomicin in treating C. difficile-associated diarrhea have been demonstrated in pediatric patients from 6 months up to less than 18 years of age. Evidence supporting its use in these age groups comes from well-controlled adult studies as well as pediatric pharmacokinetic, safety, and efficacy data.
The safety and efficacy of fidaxomicin have not been established in pediatric patients <6 months of age.
Similar to adults, fidaxomicin has minimal systemic absorption following oral administration across all age groups in pediatric patients.
Available data regarding use of fidaxomicin in pregnant women are insufficient to inform any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes.
In embryofetal reproduction studies in rats and rabbits, there was no evidence of harm to the fetus when IV fidaxomicin was administered during organogenesis at dosages resulting in fidaxomicin and OP-1118 (its main metabolite) exposures that were at least 65-fold higher than human exposures reported with the recommended dosage of the drug.
It is not known whether fidaxomicin or its main metabolite (OP-1118) is distributed into human milk, affects the breast-fed infant, or affects milk production.
The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for fidaxomicin and potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
Dosage adjustment is not recommended in geriatric patients.
In controlled trials evaluating safety and efficacy of fidaxomicin, 50% of enrolled patients were 65 years of age and older and 31% were 75 years of age and older. No overall differences in efficacy or safety of fidaxomicin compared with vancomycin were observed in geriatric patients 65 years of age or older compared with younger adults.
Although data from controlled trials indicate that plasma concentrations of fidaxomicin and its main metabolite (OP-1118) are higher in patients 65 years of age or older than in younger adults, concentrations remain in the ng/mL range. This is not considered clinically important and dosage adjustments are not recommended in geriatric patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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