Fidaxomicin

Drug overview for FIDAXOMICIN (fidaxomicin):

Generic name: FIDAXOMICIN (fye-DAX-oh-MYE-sin)
Drug class: Pseudomembranous Colitis Agents
Therapeutic class: Anti-Infective Agents

Fidaxomicin is a macrocycle antibiotic classified as a macrolide.

No enhanced Uses information available for this drug.

DRUG IMAGES

FIDAXOMICIN 200 MG TABLET

The following indications for FIDAXOMICIN (fidaxomicin) have been approved by the FDA:

Indications:
Clostridioides difficile infection

Professional Synonyms:
Antibiotic-associated colitis
Antibiotic-induced pseudomembranous enterocolitis
C. diff. infection
C. difficile colitis
Clostridioides difficile-associated diarrhea
Clostridium difficile infection
Clostridium difficile-associated diarrhea
Clostridium enterocolitis
Diarrhea associated with pseudomembranous colitis
Pseudomembranous colitis
Pseudomembranous enteritis

Dosing information for FIDAXOMICIN
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FIDAXOMICIN 200 MG TABLET	Maintenance	Adults take 1 tablet (200 mg) by oral route every 12 hours

Generic dosing information for FIDAXOMICIN
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FIDAXOMICIN 200 MG TABLET	Maintenance	Adults take 1 tablet (200 mg) by oral route every 12 hours

The following drug interaction information is available for FIDAXOMICIN (fidaxomicin):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Sodium Iodide I 131/Myelosuppressives; Immunomodulators 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)	HICON, SODIUM IODIDE I-131
Fecal Microbiota Spores/Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. 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.	VOWST

Drug Interaction

Drug Names

Sodium Iodide I 131/Myelosuppressives; Immunomodulators

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)

HICON, SODIUM IODIDE I-131

Fecal Microbiota Spores/Antibiotics

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

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.

VOWST

There are 0 moderate interactions.

Moderate List
No disease contraindications

The following adverse reaction information is available for FIDAXOMICIN (fidaxomicin):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects reported in 2% or more of patients receiving fidaxomicin in clinical trials include nausea (11%), vomiting (7%), abdominal pain (6%), GI hemorrhage (4%), anemia (2%), and neutropenia (2%). Abdominal distension, abdominal tenderness, dyspepsia, dysphagia, flatulence, intestinal obstruction, megacolon, increased blood alkaline phosphatase, decreased blood bicarbonate, increased hepatic enzymes, decreased platelet count, hyperglycemia, metabolic acidosis, drug eruption, pruritus, and rash were reported in less than 2% of patients.

There are 7 severe adverse reactions.

More Frequent	Less Frequent
None.	Gastrointestinal hemorrhage

Rare/Very Rare
Angioedema Dyspnea Gastrointestinal obstruction Head and neck angioedema Megacolon Metabolic acidosis

There are 12 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Nausea Vomiting	Anemia Neutropenic disorder

Rare/Very Rare
Abdominal distension Dyspepsia Dysphagia Flatulence Hyperglycemia Pruritus of skin Skin rash

The following precautions are available for FIDAXOMICIN (fidaxomicin):

Pediatric
Pregnant
Lactation
Geriatric

The manufacturer states that safety and efficacy of fidaxomicin have not been established in patients younger than 18 years of age. Fidaxomicin is designated an orphan drug by FDA for treatment of CDI in pediatric patients+. In a phase 2a clinical trial that evaluated the safety and pharmacokinetics of oral fidaxomicin in pediatric patients 6 months of age or older+ with C.

difficile-associated diarrhea, the safety profile of the drug was similar to that reported in adults. The most common adverse effects reported in these pediatric patients were vomiting, fever, upper abdominal pain, and C. difficile colitis requiring hospitalization after study enrollment.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

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.

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 adults 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.

Clostridioides difficile infection
A04.7	Enterocolitis due to clostridium difficile
A04.71	Enterocolitis due to clostridium difficile, recurrent
A04.72	Enterocolitis due to clostridium difficile, not specified as recurrent