Dificid (fidaxomicin)

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).

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.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

There are no moderate interactions for this drug.

*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.

• No disease contraindications

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.

Less Frequent

• Gastrointestinal hemorrhage

Rare or Very Rare

• Angioedema
• Dyspnea
• Gastrointestinal obstruction
• Head and neck angioedema
• Megacolon
• Metabolic acidosis

More Frequent

• Acute abdominal pain
• Nausea
• Vomiting

Less Frequent

• Anemia
• Neutropenic disorder

Rare or Very Rare

• Abdominal distension
• Dyspepsia
• Dysphagia
• Flatulence
• Hyperglycemia
• Pruritus of skin
• Skin rash

No enhanced messaging available.

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.