Fidaxomicin is indicated for the treatment of Clostridium difficile-associated diarrhea (CDAD) in adults and pediatric patients.

Fidaxomicin instructions

Product Name: LuciFida

Manufacturer: Lucius Pharmaceuticals

Chinese name: Fidaxomicin

English Name: Fidaxomicin

Drug approval number: 04 L 1089/24

 

 

【Summary】

Indicated for the treatment of Clostridium difficile-associated diarrhea (CDAD) in adults and pediatric patients.

【Indications】

1. Clostridium difficile-associated diarrhea

Fidaxomicin is indicated for the treatment of Clostridium difficile-associated diarrhea (CDAD) in adults and children 6 months of age and older.

2. Use

To reduce the development of resistant bacteria and maintain the effectiveness of fidaxomicin and other antimicrobial agents, fidaxomicin should be used only to treat infections proven or strongly suspected to be caused by C. difficile. If culture and susceptibility information is available, this information should be considered when selecting or modifying antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may help in the empirical selection of therapy.

 

【Specification】

200mg/tablet, 20 tablets/bottle

【 Usage and Dosage 】

1. Important management instructions

Fidaxomicin is available as a 200 mg tablet for oral administration and as a granules oral suspension (40 mg/mL (200 mg/5 mL) when reconstituted). Fidaxomicin may be taken orally with or without food.

 

2. Adult patients

The recommended dose for adults is one 200 mg fidaxomicin tablet taken orally twice daily for 10 days.

3. Children (6 months to under 18 years old)

1) Tablets

The recommended dose for pediatric patients who weigh at least 12.5 kg and are able to swallow tablets is one 200 mg fidaxomicin tablet taken orally twice daily for 10 days. If unable to swallow tablets, fidaxomicin oral suspension may be given to pediatric patients as recommended in the table below.

2) Oral suspension

The recommended dosage for pediatric patients based on weight is shown in the table below. Take Fidaxomicin Oral Suspension orally using an oral dosing syringe twice daily for 10 days.

Table: Recommended doses of Fidaxomicin oral suspension in pediatric patients (based on body weight)

Recommended Dosage of Fidaxomicin Oral Suspension in Pediatric Patients (Based on Weight)

 

4. Preparation and administration of fidaxomicin oral suspension

1) Preparation

a. Shake the glass bottle to ensure that the particles move freely and there are no clumps.

b. Take 130 ml of purified water, add it to the glass bottle and cover it with a lid.

c. Keep the bottle in a horizontal position and shake the bottle vigorously in this position for at least 2 minutes.

d. Verify that a homogenous suspension is obtained. If not, repeat the shaking step.

e. After visually confirming that the suspension is uniform, shake it for another 30 seconds.

f. Let the bottle sit for 1 minute.

g. Verify that the suspension is still homogeneous. If not, repeat steps a through f.

h. Once reconstituted, Fidaxomicin Oral Suspension is white to yellow-white in color.

i. Write the expiration date (current date plus 12 days) on the bottle.

 

2) Storage of reconstituted oral suspension

Store the reconstituted oral suspension in a refrigerator at 2°C-8°C for up to 12 days. Discard after 12 days.

 

3) Management

1. Remove the vial from the refrigerator 15 minutes before each dose.

2. Shake vigorously until the suspension has a uniform consistency.

3. Remove the cap and use the oral administration syringe to administer orally with or without food.

4. Between doses, replace cap and store in refrigerator.

 

【 Adverse Reactions 】

1. Clinical trial experience

Because clinical trials are conducted under a wide variety of conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

1) Adults

The safety of fidaxomicin 200 mg tablets was evaluated in 564 adult patients with CDAD in two active controlled trials, of whom 86.7% received a full course of treatment.

Thirty-three adult patients (5.9%) treated with fidaxomicin withdrew from the trial due to adverse reactions (ARs). The types of ARs leading to study withdrawal varied widely. Vomiting was the major adverse reaction leading to dosing discontinuation; it occurred in 0.5% of both fidaxomicin and vancomycin patients in the Phase 3 trial. The following table lists the most common selected adverse reactions occurring in ≥2% of adult patients treated with fidaxomicin.

 

Table: Selected Adverse Reactions Reported in ≥2% of Adult Patients Treated with Fidaxomicin in Controlled Trials

Selected adverse reactions reported in ≥ 2% of adult patients receiving fidaxomicin in controlled trials

In controlled trials, the following adverse reactions were reported in < 2% of adult patients taking fidaxomicin tablets:

Gastrointestinal disorders: abdominal distension, abdominal tenderness, indigestion, dysphagia, flatulence, intestinal obstruction, megacolon

Immune disorders: elevated blood alkaline phosphatase, decreased blood bicarbonate, increased liver enzymes, decreased platelet count

Metabolic and nutritional disorders: hyperglycemia, metabolic acidosis

Skin and subcutaneous tissue disorders: drug eruption, pruritus, rash

2) Pediatrics

The safety of fidaxomicin was evaluated in pediatric patients aged 6 months to less than 18 years in a phase 2 single-arm trial of 38 patients and in a phase 3 randomized, active-controlled trial of 98 patients treated with fidaxomicin and 44 patients treated with vancomycin. In both studies, patients took fidaxomicin orally twice daily for 10 days. Patients who were < 2 years old, or weighed < 12.5 kg, or were unable to swallow tablets received weight-based dosing of fidaxomicin oral suspension. Patients who weighed at least 12.5 kg and were able to swallow tablets received 200 mg fidaxomicin tablets. The age range was 11 months to 17 years in the phase 2 trial and 1 month to 17 years (1 patient was younger than 6 months) in the phase 3 trial.

In the phase 2 single-arm trial, there was one death. In the phase 3 trial, there were three deaths during the study period (40 days) in patients treated with fidaxomicin and no deaths in patients treated with vancomycin. All deaths occurred in patients younger than 2 years of age and appeared to be related to underlying comorbidities.

In the Phase 2 trial, 7.9% (3/38) of patients discontinued treatment due to adverse reactions; in the Phase 3 trial, 1% (1/98) of patients treated with fidaxomicin and 2.3% (1/44) of patients treated with vancomycin discontinued treatment due to adverse reactions. The following table lists the most common selected adverse reactions occurring in ≥5% of pediatric patients treated with fidaxomicin in the Phase 3 trial.

 

Table: Selected Adverse Reactions Reported in ≥5% of Pediatric Patients Treated with Fidaxomicin in Controlled Trials

* Includes abdominal pain, lower abdominal pain, and upper abdominal pain

† Includes elevated alanine aminotransferase, elevated aspartate aminotransferase, and elevated liver enzymes

‡ Includes rash, follicular rash, maculopapular rash, and exfoliative rash

The following adverse reactions were reported in < 5% of pediatric patients taking fidaxomicin in clinical trials: Skin and subcutaneous tissue disorders: urticaria, pruritus

 

2. Post-launch experience

The following adverse reactions have been identified during postapproval use of fidaxomicin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergic reactions (dyspnea, angioedema, rash, itching)

 

【 Notes 】

1. Allergic reaction

Acute hypersensitivity reactions, including dyspnea, rash, pruritus, and angioedema of the mouth, throat, and face, have been reported with fidaxomicin. If a serious hypersensitivity reaction occurs, fidaxomicin should be discontinued and appropriate treatment initiated.

Some patients who have experienced allergic reactions to fidaxomicin have also reported a history of allergic reactions to other macrolides. Physicians prescribing fidaxomicin to patients with known macrolide allergies should be aware of the possibility of allergic reactions.

 

2. Not suitable for infections other than Clostridium difficile-associated diarrhea

Because of minimal systemic absorption of fidaxomicin, fidaxomicin is not expected to be effective for the treatment of other types of infections. Fidaxomicin has not been studied for the treatment of infections other than CDAD. Fidaxomicin should be used only for the treatment of CDAD disease.

 

3. Research progress on drug-resistant bacteria

Prescribing fidaxomicin in the absence of proven or strongly suspected C. difficile infection is unlikely to provide benefit to the patient and may increase the risk of the development of resistant bacteria.

 

【 Use in special populations 】

1. Pregnancy

Available data on the use of fidaxomicin in pregnant women are limited and insufficient to inform any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Embryo-fetal reproduction studies in animals administered intravenously during the period of organogenesis showed no evidence of fetal harm at exposures of fidaxomicin and OP-1118 (its major metabolite) 65 times or more above the clinical exposure at the recommended dose of fidaxomicin.

 

2. Lactation

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

 

3. Use by Children

The safety and efficacy of fidaxomicin for the treatment of CDAD have been demonstrated in pediatric patients aged 6 months to less than 18 years. The use of fidaxomicin in these age groups is supported by evidence from adequate and well-controlled trials of fidaxomicin in adult patients with CDAD and from pharmacokinetic, safety, and efficacy data from pediatric trials. In pediatric trials, no new safety signals were identified related to the use of fidaxomicin in pediatric patients.

The safety and effectiveness of fidaxomicin have not been established in pediatric patients younger than 6 months of age.

 

4. Medication for the elderly

Of the total number of patients in the fidaxomicin-controlled trials, 50% were 65 years of age and older and 31% were 75 years of age and older. No overall differences in the safety or effectiveness of fidaxomicin were observed between these subjects and younger subjects compared with vancomycin.

In controlled trials, compared with non-elderly (

 

【 Contraindications 】

Contraindicated in patients with known hypersensitivity to fidaxomicin or any other component of fidaxomicin.

 

【 Drug Interactions 】

Fidaxomicin and its major metabolite OP-1118 are substrates for the efflux transporter P-glycoprotein (P-gp) expressed in the gastrointestinal tract.

1. Cyclosporine

Cyclosporine is an inhibitor of multiple transporters, including P-gp. When cyclosporine was co-administered with fidaxomicin, plasma concentrations of fidaxomicin and OP-1118 increased significantly but remained in the ng/mL range. It is also possible that fidaxomicin and OP-1118 concentrations were reduced at the site of action (i.e., the gastrointestinal tract) through P-gp inhibition; however, in controlled clinical trials, co-administration of P-gp inhibitors had no attributable effects on safety or treatment outcomes in adult patients treated with fludaxomicin. Based on these results, fidaxomicin can be co-administered with P-gp inhibitors, and no dose adjustment is recommended.

 

【 Overdose 】

No cases of acute overdose have been reported in humans. No drug-related adverse effects were observed in dogs given fidaxomicin tablets at a dose of 9600 mg/day (more than 100 times the human dose, by weight) for 3 months.

 

【 Element 】

Active ingredient:fidaxomicin

Tablets: Film-coated tablets, each containing 200 mg of fidaxomicin and the following inactive ingredients: butylated hydroxytoluene, hydroxypropylcellulose, lecithin (soy), magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, sodium starch glycolate, talc, and titanium dioxide.

 

【 Properties 】

tablet

 

【 Storage method 】

Fidaxomicin Tablets

Storage temperature is 20°C-25°C; excursions to 15°C-30°C permitted. See USP Controlled Room Temperature. Store in original bottle.