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Fidaxomicin: Drug information

Fidaxomicin: Drug information
(For additional information see "Fidaxomicin: Patient drug information" and see "Fidaxomicin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Dificid
Brand Names: Canada
  • Dificid
Pharmacologic Category
  • Antibiotic, Macrolide
Dosing: Adult
Clostridioides difficile infection, treatment

Clostridioides difficile infection, treatment:

Note: For initial and recurrent nonfulminant infection (ACG [Kelly 2021b]; IDSA/SHEA [Johnson 2021]). If antibiotic(s) for a primary infection are essential, some experts extend C. difficile infection treatment one week beyond other antibiotic(s) (Kelly 2021a).

Initial infection: Oral: 200 mg twice daily for 10 days (ACG [Kelly 2021b]; IDSA/SHEA [Johnson 2021]). If delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (IDSA/SHEA [McDonald 2018]).

Recurrent infection: Oral: 200 mg twice daily for 10 days or 200 mg twice daily for 5 days, followed by 200 mg once every other day for 20 days (IDSA/SHEA [Johnson 2021]).

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary (minimal systemic absorption).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's label (has not been studied); However, due to minimal systemic absorption no dosage adjustment predicted.

Dosing: Pediatric

(For additional information see "Fidaxomicin: Pediatric drug information")

Clostridioides difficile infection, treatment

Clostridioides difficile infection (CDI), treatment: Note: Fidaxomicin is only recommended in the setting of multiple recurrences in pediatric patients, as data and experience are limited (IDSA/SHEA [McDonald 2018]). In patients ≥18 years, fidaxomicin is recommended as a first-line treatment option for an initial episode (IDSA/SHEA [McDonald 2018]).

Weight-directed dosing: Limited data available: Infants ≥6 months and Children: Oral: 16 mg/kg/dose twice daily for 10 days; maximum dose: 200 mg/dose (O'Gorman 2018; Wolf 2019). Dosing based on a multi-center, randomized, phase 3 trial comparing fidaxomicin to vancomycin in the treatment of CDI (n=142 [98 received fidaxomicin]; median age: 60 months [interquartile range: 24 to 132 months]); in the trial, patients ≥6 years received a fixed dose of 200 mg twice daily. Most efficacy endpoints, including clinical cure, were statistically similar between treatment groups, with a higher end of study cure rate seen in the fidaxomicin group; adverse events were similar between groups (Wolf 2019).

Fixed dosing: Infants ≥6 months, Children, and Adolescents:

4 to <7 kg: Oral: Oral suspension: 80 mg twice daily for 10 days.

7 to <9 kg: Oral: Oral suspension: 120 mg twice daily for 10 days.

9 to <12.5 kg: Oral: Oral suspension: 160 mg twice daily for 10 days.

≥12.5 kg: Oral: Oral suspension, tablets: 200 mg twice daily for 10 days.

Dosing: Kidney Impairment: Pediatric

No dosage adjustment necessary (minimal systemic absorption).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, dosage adjustment is likely unnecessary due to low systemic absorption and lack of hepatic metabolism or elimination of parent compound and metabolite (O'Gorman 2018; Wolf 2019).

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Reconstituted, Oral:

Dificid: 40 mg/mL (136 mL) [contains sodium benzoate; mixed berry flavor]

Tablet, Oral:

Dificid: 200 mg [contains soybean lecithin]

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Dificid: 200 mg [contains soybean lecithin]

Administration: Adult

Oral: May be administered with or without food.

Suspension: Remove from refrigerator 15 minutes prior to each administration. Shake vigorously before use; use oral dosing syringe for administration.

Administration: Pediatric

Oral: May be administered with or without food.

Oral suspension: Remove bottle from refrigerator 15 minutes prior to each dose. Shake vigorously prior to measuring dose and check for even consistency. Measure and administer using an oral dosing syringe.

Tablet: Tablets may be crushed and mixed with 40 mL of water or applesauce, or 60 mL of Ensure for immediate administration (Tousseeva 2014).

G-tube/NG: Very limited experience reported; minimal product loss was observed after a single tablet was crushed, mixed into 40 mL of water, and passed through an NG tube followed by a water flush (Tousseeva 2014). In 1 case report, fidaxomicin tablets were crushed, mixed with water, and administered via G-tube to a 10 year old; clinical improvement was observed (Smeltzer 2013).

Use: Labeled Indications

Clostridioides difficile infection, treatment: Treatment of C. difficile infection (CDI) in adult and pediatric patients ≥6 months of age.

Medication Safety Issues
Sound-alike/look-alike issues:

Fidaxomicin may be confused with rifAXIMin.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Nausea (adults 11%)

Miscellaneous: Fever (infants, children, and adolescents: 13%)

1% to 10%:

Dermatologic: Pruritus (<5%), skin rash (adults: <2%), urticaria (infants, children, and adolescents: <5%)

Endocrine & metabolic: Decreased serum bicarbonate (adults: <2%), hyperglycemia (adults: <2%), metabolic acidosis (adults: <2%)

Gastrointestinal: Abdominal distention (adults: <2%), abdominal pain (6% to 8%), abdominal tenderness (adults: <2%), constipation (infants, children, and adolescents: 5%), diarrhea (infants, children, and adolescents: 7%), dyspepsia (adults: <2%), dysphagia (adults: <2%), flatulence (adults: <2%), gastrointestinal hemorrhage (adults: 4%), intestinal obstruction (adults: <2%), non-Hirschsprung megacolon (adults: <2%), vomiting (7%)

Hematologic & oncologic: Anemia (adults: 2%), decreased platelet count (adults: <2%), neutropenia (adults: 2%)

Hepatic: Increased liver enzymes (adults: ≤5%), increased serum alkaline phosphatase (adults: <2%), increased serum transaminases (infants, children, and adolescents: 5%)

Hypersensitivity: Fixed drug eruption (adults: <2%)

Postmarketing:

Hepatic: Hepatotoxicity (idiosyncratic) (Chalasani 2014)

Hypersensitivity: Angioedema, hypersensitivity reaction

Contraindications

Hypersensitivity to fidaxomicin or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity reactions (angioedema [mouth, face, throat], dyspnea, pruritus, and rash) to fidaxomicin have been reported. If a severe reaction occurs, discontinue drug and institute supportive care.

• Macrolide allergy: Use with caution in patients with a history of macrolide allergy; may be at increased risk for hypersensitivity.

Other warnings/precautions:

• Appropriate use: Do not use for systemic infections; fidaxomicin systemic absorption is negligible. Use only in patients with proven or strongly suspected C. difficile infections.

Metabolism/Transport Effects

Substrate of P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Mizolastine: Macrolide Antibiotics may increase the serum concentration of Mizolastine. Risk X: Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Pregnancy Considerations

The limited systemic absorption of fidaxomicin may limit potential fetal exposure.

Breastfeeding Considerations

It is not known if fidaxomicin is present in breast milk.

The limited systemic absorption of fidaxomicin may limit potential distribution into breast milk.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Mechanism of Action

Inhibits RNA polymerase sigma subunit resulting in inhibition of protein synthesis and cell death in susceptible organisms including C. difficile; bactericidal

Pharmacokinetics

Note: The pharmacokinetics of fidaxomicin in pediatric patients 6 months to <18 years of age are similar to those in adult patients (O'Gorman 2018; Wolf 2019).

Absorption: Oral: Minimal systemic absorption.

Distribution: Largely confined to the gastrointestinal tract; in single- and multiple-dose studies, fecal concentrations of fidaxomicin and its active metabolite (OP-1118) are very high while serum concentrations are minimally detectable to undetectable.

Metabolism: Intestinal hydrolysis to less active metabolite (OP-1118).

Excretion: Feces (>92% as unchanged drug and metabolites); urine (<1% as metabolite).

Pharmacokinetics: Additional Considerations

Older adult: Plasma concentrations were approximately 2- to 4-fold higher in elderly patients versus nonelderly patients.

Pricing: US

Suspension (reconstituted) (Dificid Oral)

40 mg/mL (per mL): $39.49

Tablets (Dificid Oral)

200 mg (per each): $268.51

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Dafclir (JP);
  • Dificid (AU, BB, TW);
  • Dificlir (AT, BE, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, HR, HU, IE, IL, IS, LB, LT, LU, LV, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR)


For country code abbreviations (show table)
  1. Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-966. [PubMed 24935270]
  2. Dificid (fidaxomicin) [prescribing information] Rahway, NJ: Merck Sharp & Dohme LLC; June 2022.
  3. Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021;73(5):e1029-e1044. doi:10.1093/cid/ciab549 [PubMed 34164674]
  4. Kelly CP, Lamont JT, Bakken JS. Clostridioides difficile infection in adults: Treatment and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 25, 2021a.
  5. Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021b;116(6):1124-1147. doi:10.14309/ajg.0000000000001278 [PubMed 34003176]
  6. Louie TJ, Emery J, Krulicki W, et al. OPT-80 Eliminates Clostridium difficile and Is Sparing of Bacteroides Species During Treatment of C. difficile Infection. Antimicrob Agents Chemother. 2009;53(1):261-263. [PubMed 18955523]
  7. Louie TJ, Miller MA, Crook DW, et al. Effect of Age on Treatment Outcomes in Clostridium difficile Infection. J Am Geriatr Soc. 2013;61(2):222-230. [PubMed 23379974]
  8. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin Versus Vancomycin for Clostridium difficile Infection. N Engl J Med. 2011;364(5):422-431. [PubMed 21288078]
  9. Louie T, Miller M, Donskey C, et al. Clinical Outcomes, Safety, and Pharmacokinetics of OPT-80 in a Phase 2 Trial With Patients With Clostridium difficile Infection. Antimicrob Agents Chemother. 2009;53(1):223-238. [PubMed 18955525]
  10. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085 [PubMed 29462280]
  11. O'Gorman MA, Michaels MG, Kaplan SL, et al. Safety and pharmacokinetic study of fidaxomicin in children with Clostridium difficile-associated diarrhea: a phase 2a multicenter clinical trial. J Pediatric Infect Dis Soc. 2018;7(3):210-218. [PubMed 28575523]
  12. Shue YK, Sears PS, Shangle S, et al. Safety, Tolerance, and Pharmacokinetic Studies of OPT-80 in Healthy Volunteers Following Single and Multiple Oral Doses. Antimicrob Agents Chemother. 2008;52(4):1391-1395. [PubMed 18268081]
  13. Smeltzer S, Hassoun A. Successful use of fidaxomicin in recurrent Clostridium difficile infection in a child. J Antimicrob Chemother. 2013;68(7):1688-1689. [PubMed 23463209]
  14. Sullivan KM, Spooner LM. Fidaxomicin: A Macrocyclic Antibiotic for the Management of Clostridium difficile Infection. Ann Pharmacother. 2010;44(2):352-359. [PubMed 20071495]
  15. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections. Am J Gastroenterol. 2013;108(4):478-498. [PubMed 23439232]
  16. Tannock GW, Munro K, Taylor C, et al. A New Macrocyclic Antibiotic, Fidaxomicin (OPT-80), Causes Less Alteration to the Bowel Microbiota of Clostridium difficile-Infected Patients Than Does Vancomycin. Microbiology. 2010;156(pt 11):3354-3359. [PubMed 20724385]
  17. Tousseeva A, Jackson JD, Redell M, et al. Stability and recovery of DIFICID(®) (fidaxomicin) 200-mg crushed tablet preparations from three delivery vehicles, and administration of an aqueous dispersion via nasogastric tube. Drugs R D. 2014;14(4):309-314. doi:10.1007/s40268-014-0067-3 [PubMed 25424419]
  18. Wolf J, Kalocsai K, Fortuny C, et al. Safety and efficacy of fidaxomicin and vancomycin in children and adolescents with Clostridioides (Clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (SUNSHINE). Clin Infect Dis. Published online November 27, 2019. [PubMed 31773143]
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