Drug information of Fidaxomicin

Fidaxomicin

Drug group:

Fidaxomicin is indicated for the treatment of Clostridioides (formerly Clostridiumdifficile-associated diarrhea in adult and pediatric patients 6 months of age and older.

Fidaxomicin 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.

Mechanism of effect

Macrolide antibiotic that inhibits RNA synthesis by binding to RNA polymerases

Bactericidal against C difficile in vitro; demonstrates a postantibiotic effect vs C difficile of 6-10 hr

Pharmacodynamic

Fidaxomicin 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.

Pharmacokinetics

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

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)

Elimination

Half-life: 9 hr

Excretion: Feces (92%)

Drug indications

Clostridium difficile

Dosage

Indicated for treatment of Clostridioides difficile-associated diarrhea (CDAD)

200 mg PO BID x10 days

Drug contraindications

Hypersensitivity to this drug

Alerts

Not indicated for systemic infections owing to minimal systemic absorption

Only use for infection proven or strongly suspected to be caused by C difficile to avoid development of drug resistant bacteria; therapy not effective for treatment of other types of infections due to minimal systemic absorption of fidaxomicin

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

Use in the absence of proven or strongly suspected C difficile infection is unlikely to provide benefit to the patient and increases risk of developing drug-resistant bacteria
Prolonged cardiac repolarization and QT interval have been reported in patients receiving treatment with macrolides

Points of recommendation

Oral Suspension Preparation

Shake glass bottle to ensure granules move around freely and no caking has occurred

Measure 130 mL of purified water, add to glass bottle, and cap tightly

Hold bottle in horizontal position and shake bottle vigorously in that position for at least 2 minutes

Verify homogeneous suspension obtained; if not, repeat shaking

Once homogeneous suspension is visually confirmed, shake an additional 30 seconds

Let bottle stand for 1 minute

Verify that the suspension is still homogeneous; if not, repeat shaking instructions

Once reconstituted, oral suspension is white to yellowish white in color

Write discard date (current date plus 12 days) on the bottle

Oral Administration

May take with or without food

Oral suspension

  • Remove bottle from refrigerator 15 minutes before administration
  • Shake vigorously until suspension has an even consistency
  • Remove cap, then administer orally with or without food using an oral dosing syringe
  • Between doses, replace cap and refrigerate

Storage

Tablets

  • 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
  • Store in the original bottle

Oral suspension

  • Unreconstituted granules
    • 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
    • Store in the original package; do not open pouch until time of use
  • Reconstituted suspension
    • Refrigerate at 36-46ºF (2-8ºC) for up to 12 days
    • Store capped in the original bottle

Pregnancy level

HAVE NOT BEEN ESTABLISHED

Pregnancy

Limited available data in pregnant women are insufficient to inform any drug-associated risk for major birth defects; miscarriage or adverse maternal or fetal outcomes

Animal data

  • Embryo-fetal reproduction studies in rats and rabbits dosed intravenously during organogenesis revealed no evidence of harm to fetus at exposures 65-fold or higher than the clinical exposure at the recommended dose

Breast feeding warning

There is no information on presence of fidaxomicin or its main metabolite, OP-1118, in human milk, the effects on breastfed infant, or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from the underlying maternal condition

Drug forms

Dificid

Ask a Pharmacist


User's questions
    No comments yet.