Fidaxomicin

Pronunciation: fye-DAX-oh-MYE-sin
Class: Macrolide

Trade Names

Dificid
- Tablets 200 mg

Pharmacology

Bactericidal against Clostridium difficile in vitro, inhibiting RNA synthesis by RNA polymerases.

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Pharmacokinetics

Absorption

Minimal systemic absorption. C _max was approximately 5.2 ng/mL and T _max was approximately 2 h (range, 1 to 5 h). C _max of fidaxomicin and OP-1118 (its main metabolite) decreased by 21.5% and 33.4%, respectively, when administered with a high-fat meal, which is not considered clinically significant.

Distribution

Mostly confined to GI tract.

Metabolism

Transformed by hydrolysis at the isobutyryl ester to form its main active metabolite (OP-1118).

Elimination

Mainly excreted in feces (more than 92% as fidaxomicin and OP-1118) and very little in urine (0.59% of dose recovered). Elimination half-life was approximately 11.7 h (fidaxomicin) and 11.2 h (OP-1118 metabolite).

Special Populations

Plasma concentrations did not vary by severity of renal impairment. No dosage adjustment is recommended based on renal function.

Pharmacokinetics have not been evaluated in hepatic impairment.

Plasma concentrations were approximately 2- to 4-fold higher in elderly patients versus nonelderly patients. No dosage adjustment is recommended for elderly patients.

Plasma concentration did not vary by gender. No dosage adjustment is necessary based on gender.

Indications and Usage

For treatment of C. difficile –associated diarrhea (CDAD).

Contraindications

None well documented.

Dosage and Administration

PO 200 mg twice daily for 10 days.

General Advice

• May administer with or without food.

Storage/Stability

Store between 68° and 77°F; excursions are permitted between 59° and 86°F.

Drug Interactions

Coadministration of cyclosporine, a P-glycoprotein (Pgp) inhibitor, may increase plasma concentrations of fidaxomicin and its metabolite, OP-1118. In addition, concentrations of fidaxomicin and OP-1118 may be reduced at the site of action (ie, GI tract) via Pgp inhibition. However, cyclosporine does not appear to affect the safety or treatment outcome of fidaxomicin. Fidaxomicin may be coadministered with Pgp inhibitors and no dose adjustment is recommended.

Administration of fidaxomicin with a high-fat meal decreases the C _max of fidaxomicin and OP-1118, while the AUC is unchanged compared with administration under fasting conditions. The magnitude of the decrease in C _max is not considered to be clinically important. Fidaxomicin may be given without respect to food.

Adverse Reactions

Dermatologic

Drug eruption, pruritus, rash (less than 2%).

GI

Nausea (11%); vomiting (7%); abdominal pain (6%); GI hemorrhage (4%); abdominal distension, abdominal tenderness, dyspepsia, dysphagia, flatulence, intestinal obstruction, megacolon (less than 2%).

Hematologic

Anemia, neutropenia (2%).

Lab Tests

Decreased blood bicarbonate, decreased platelet count, increased blood alkaline phosphatase, increased hepatic enzymes (less than 2%).

Metabolic-Nutritional

Hyperglycemia, metabolic acidosis (less than 2%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy in patients younger than 18 y have not been established.

Renal Function

No dosage adjustment is recommended based on renal function.

Systemic infections

Because there is minimal systemic absorption, fidaxomicin is not effective for treatment of systemic infections.

Patient Information

• Inform patients that fidaxomicin tablets may be taken with or without food.
• Remind patients that fidaxomicin is an antibiotic that should only be used to treat bacterial infections and does not treat viral infections.
• Advise patients that the drug only treats CDAD and should not be used to treat any other infection.
• Inform patients that it is common to feel better early in the course of therapy and to take the medication exactly as directed. Skipping doses or not completing the full course of therapy may decrease the effectiveness of treatment and increase the likelihood that bacteria will develop resistance and will not be treatable by fidaxomicin or other antibacterial drugs in the future.

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