dificlir
dificlir Uses, Dosage, Side Effects, Food Interaction and all others data.
dificlir is a novel macrolide antibiotic used in the treatment of diarrhea caused by Clostridioides (formerly Clostridium) difficile in adult and pediatric patients over the age of 6 months. dificlir is a naturally-occurring 18-member macrocycle derived from fermentation. Because fidaxomicin contains an 18-membered lactone ring in its structure, it is referred to as a macrocyclic lactone antibiotic drug. The antibacterial activity of fidaxomicin is distinct from macrolides and rifamycins, as the bactericidal activity is time-dependent, and not concentration-dependent. dificlir was the first macrocyclic lactone antibiotic with activity against C. difficile, and it displays a narrow spectrum of activity against gram-positive anaerobes. It mediates its potent bactericidal action on the bacteria by inhibiting the bacterial RNA synthase, thereby disrupting bacterial transcription. The minimum inhibitory concentration (MIC90) for fidaxomicin is four times less than that of vancomycin, which was the primary drug of choice for C. difficile infection before the approval of fidaxomicin. Unlike vancomycin, however, fidaxomicin has a negligible effect on normal colonic microflora.
The FDA initially approved fidaxomicin in May 2011 for the treatment of C. difficile-associated diarrhea in adult patients over the age of 18. Later that year in December, the drug was also approved by the European Medicine Agency. In June 2012, fidaxomicin was also granted approval by Health Canada. The approved indication of fidaxomicin was expanded by the FDA in January 2020 to include pediatric patients over the age of 6 months in the treatment population.
dificlir has a narrow-spectrum antibacterial profile, with potent bactericidal activity specifically against C. difficile. The minimum inhibitory concentration for 90% of organisms for fidaxomicin against C. difficile ranged from 0.0078 to 2 μg/mL in vitro. The bactericidal activity of fidaxomicin is time-dependent. Other than C. difficile, fidaxomicin has moderate inhibitory activity against Gram-positive bacteria (S. aureus and Enterococcus spp.) and poor activity against normal colonic flora, including anaerobes and enteric Gram-negative bacilli. Isolates of C. difficile that are resistant to rifamycins or other antimicrobial classes (such as cephalosporins, fluoroquinolones, clindamycin) were not shown to be cross-resistant to fidaxomicin.
| Trade Name | dificlir |
| Availability | Prescription only |
| Generic | Fidaxomicin |
| Fidaxomicin Other Names | Difimicin, Fidaxomicin, Fidaxomicina, Lipiarmicin, Lipiarmycin, Lipiarrmycin, Tiacumicin B |
| Related Drugs | metronidazole, vancomycin, Flagyl, penicillin v potassium, Acidophilus, lactobacillus acidophilus |
| Weight | 200mg, |
| Type | Tablet, Film Coated |
| Formula | C52H74Cl2O18 |
| Weight | Average: 1058.05 Monoisotopic: 1056.4252209 |
| Protein binding | Since fidaxomicin has minimal systemic absorption following oral administration, there is limited information on the plasma protein binding profile of fidoxamicin. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | Astellas Pharma Europe B,v,, Tillotts Pharma Uk Limited |
| Available Country | Saudi Arabia, United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
dificlir is a macrolide antibiotic used to treat diarrhea associated with Clostridium difficile infection.
dificlir is indicated for the treatment of Clostridioides (formerly Clostridium) difficile-associated diarrhea in adult and pediatric patients 6 months of age and older.
dificlir should only be used in patients with proven or strongly suspected C. difficile infection to reduce the risk of development of drug-resistant bacteria and maximize the therapeutic effectiveness of fidaxomicin and other antimicrobial agents.
dificlir is also used to associated treatment for these conditions: Clostridium Difficile-Associated Diarrhea (CDAD)
How dificlir works
Clostridium difficile is a Gram-positive bacterium that causes various gastrointestinal complications, such as antibiotic-associated diarrhea. C. difficile infection can be caused by antibiotic therapy, resulting in the disruption of the human gut flora leads to an overgrowth of C. difficile. The consequences of C. difficile infection can be mild to severe and sometimes fatal.
dificlir gets hydrolyzed to its active metabolite, OP-1118, upon oral administration. Both compounds mediate a bactericidal activity against C. difficile by inhibiting bacterial RNA polymerase at the initiation phase of the transcription cycle. The RNA polymerase is an essential bacterial enzyme that regulates gene expression, catalyzes nucleic acid interactions, and promotes several bacterial enzymatic reactions critical for bacterial survival. The core RNA polymerase is composed of a complex of different subunits and contains the active site. To initiate bacterial transcription, the active site of the core RNA polymerase binds to a promoter-specificity σ initiation factor, which locates and binds to a promoter region of the DNA. The DNA-RNA polymerase interaction promotes subsequent steps of transcription, which involves the separation of DNA strands. dificlir binds to the DNA template-RNA polymerase complex, thereby preventing the initial separation of DNA strands during transcription and inhibiting messenger RNA synthesis. The narrow spectrum of antimicrobial activity of fidaxomicin may be explained by the unique target site of fidaxomicin and differing σ subunits of the core structure of RNA polymerase among bacterial species.
Toxicity
In rats, the LD50 of fidaxomicin was approximately 200 mg/kg and the no observed adverse effect level (NOAEL) was determined to be 62.5 mg/kg following administration of a single intravenous dose.
There is limited clinical data on acute overdose in humans.
Food Interaction
- Take with or without food. High-fat meal decreases the Cmax of fidaxomicin and its metabolite in a clinically insignificant way.
dificlir Drug Interaction
Unknown: contained in alcoholic beverages , dicyclomine, bumetanide, ciprofloxacin, sulfamethoxazole / trimethoprim, docusate, ubiquinone, carvedilol, metronidazole, cyclobenzaprine, fluticasone nasal, heparin, ruxolitinib, promethazine, vitamin a topical, bioflavonoids, sotalol, cyanocobalamin, alprazolam, ondansetron
dificlir Disease Interaction
Volume of Distribution
dificlir is mainly confined to the gastrointestinal tract when orally administered. There is limited information on the volume of distribution of fidaxomicin.
Elimination Route
Following oral administration of a single dose of 200 mg fidaxomicin in healthy adults, the Cmax of fidaxomicin and its main metabolite OP-1118 were 5.20 ± 2.81 ng/mL and 12.0 ± 6.06, respectively. The median Tmax of fidaxomicin was 2 hours. The systemic absorption of fidaxomicin following oral administration is minimal.
In a food-effect study involving healthy adults in either with a high-fat meal versus under fasting conditions, the Cmax of fidaxomicin and OP-1118 were decreased by 21.5% and 33.4%, respectively; however, this effect is deemed to be clinically insignificant as the therapeutic action of fidaxomicin does not depend on drug concentrations in the systemic circulation.
Half Life
Following oral administration of a single dose of 200 mg fidaxomicin in healthy adults, the elimination half-life of fidaxomicin was approximately 11.7 ± 4.80 hours.
Clearance
There is limited information on the clearance of fidaxomicin.
Elimination Route
Following oral administration, fidaxomicin is mainly excreted in feces. More than 92% of the dose was recovered in the faces as either the unchanged parent drug or metabolites in one study consisting of healthy adults receiving single doses of 200 mg and 300 mg of fidaxomicin. In another study of healthy adults, approximately 0.59% fo the oral dose (200 mg) administered was recovered in the urine as the main metabolite, OP-1118.
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