ECALTA

Anidulafungin or Eraxis is an anti-fungal drug There is preliminary evidence that it has a similar safety profile to caspofungin.

For use in the treatment of the following fungal infections: Candidemia and other forms of Candida infections (intra-abdominal abscess, and peritonitis), Aspergillus infections, and esophageal candidiasis.

Also considered an alternative treatment for oropharyngeal canaidiasis.

Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product of Aspergillus nidulans.

Anidulafungin is an echinocandin, a class of antifungal drugs that inhibits the synthesis of 1,3-β-D-glucan, an essential component of fungal cell walls.

Anidulafungin is active in vitro against many Candida, as well as some Aspergillus.

Like other echinocandins, anidulafungin is not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes.

1,3-beta-glucan synthase component FKS1 (Aspergillus niger (strain CBS 513.88 / FGSC A1513)) Inhibitor 1,3-beta-glucan synthase component GSC2 (Baker's yeast) Inhibitor.

Hepatic metabolism of anidulafungin has not been observed.

Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 (CYP450) isoenzymes.

Anidulafungin undergoes slow chemical degradation at physiologic temperature and pH to a ring-opened peptide that lacks antifungal activity.

Less than 1% of the administered radioactive dose was excreted in the urine.

Anidulafungin is not hepatically metabolized.

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During clinical trials a single 400 mg dose of anidulafungin was inadvertently administered as a loading dose.

No clinical adverse events were reported.

The maximum non-lethal dose of anidulafungin in rats was 50 mg/kg, a dose which is equivalent to 10 times the recommended daily dose for esophageal candidiasis (50 mg/day).

• Patients with known hypersensitivity to anidulafungin, any component of ERAXIS, or other echinocandins.

• Patients with known or suspected Hereditary Fructose Intolerance (HFI).

• Known hypersensitivity to anidulafungin, any component of ERAXIS, or other echinocandins.

• Known or suspected Hereditary Fructose Intolerance (HFI).

Patients 1 Month of Age and Older Candidemia and other forms of Candida infections 200 mg loading dose on Day 1, followed by 100 mg once daily maintenance dose thereafter for at least 14 days after the last positive culture 3 mg/kg (not to exceed 200 mg) loading dose on Day 1, followed by 1.5 mg/kg (not to exceed 100 mg) once daily maintenance dose thereafter for at least 14 days after the last positive culture Esophageal candidiasis 100 mg loading dose on Day 1, followed by 50 mg once daily maintenance dose thereafter for a minimum of 14 days and for at least 7 days following resolution of symptoms Not Approved Rate of Infusion for Adults and Pediatric Patients The rate of infusion should not exceed 1.1 mg/minute [equivalent to 1.4 mL/minute or 84 mL/hour when reconstituted and diluted per instructions] 2.1 Recommended Dosage in Adults Candidemia and other Candida infections (intra-abdominal abscess and peritonitis) The recommended dose is a single 200 mg loading dose of ERAXIS on Day 1, followed by a 100 mg once daily maintenance dose thereafter.

Duration of treatment should be based on the patient's clinical response.

In general, antifungal therapy should continue for at least 14 days after the last positive culture.

The recommended dose is a single 100 mg loading dose of ERAXIS on Day 1, followed by a 50 mg once daily maintenance dose thereafter.

Patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms.

Because of the risk of relapse of esophageal candidiasis in patients with HIV infection, suppressive antifungal therapy may be considered after a course of treatment. 2.2 Recommended Dosage in Pediatric Patients (1 Month of Age and Older) Candidemia and other Candida infections (intra-abdominal abscess and peritonitis) The recommended dose is a single loading dose of 3 mg/kg (not to exceed 200 mg) of ERAXIS on Day 1, followed by a once daily maintenance dose of 1.5 mg/kg (not to exceed 100 mg) of ERAXIS thereafter.

Overall antifungal treatment should continue for at least 14 days after the last positive culture. 2.3 Preparation for Administration ERAXIS for Injection must be reconstituted with sterile Water for Injection and subsequently diluted only with 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline), prior to administration.

The compatibility of reconstituted

ERAXIS with intravenous substances, additives, or medications other than 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline) has not been established.

Do NOT dilute with other solutions or co-infuse with other medications or electrolytes.

The infusion solution must not be frozen.

Reconstitution of the 50 mg/vial Aseptically reconstitute each 50 mg vial with 15 mL of sterile Water for Injection to provide a concentration of 3.33 mg/mL.

Reconstitution of the 100 mg/vial Aseptically reconstitute each 100 mg vial with 30 mL of sterile Water for Injection to provide a concentration of 3.33 mg/mL.

ERAXIS reconstituted solution can be stored at 25°C (77°F) for up to 24 hours prior to dilution into the infusion solution.

Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 24 hours at 25°C (77°F).

From a microbiological point of view, following good aseptic practices, the reconstituted solution can be utilized for up to 24 hours when stored at 25°C. 2.4 Dilution and Administration of the Infusion Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

If particulate matter or discoloration is identified, discard the solution.

Aseptically transfer the contents of the reconstituted vial(s) into the appropriately sized IV bag (or bottle) containing either 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline).

Table for the dilution to a concentration of 0.77 mg/mL for the final infusion solution and infusion instructions for each dose.

The rate of infusion should not exceed 1.1 mg/minute (equivalent to 1.4 mL/minute or 84 mL/hour when reconstituted and diluted per instructions) .

Table 1: Dilution Requirements for ERAXIS Administration Dose Number of Vials Required Total Reconstituted Volume Required Infusion Volume Either 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline) Total Infusion Volume Infusion solution concentration is 0.77 mg/mL Rate of Infusion Minimum Duration of Infusion 50 mg 1–50 mg 15 mL 50 mL 65 mL 1.4 mL/min or 84 mL/ hour 45 min 100 mg 2–50 mg or 1–100 mg 30 mL 100 mL 130 mL 1.4 mL/min or 84 mL/ hour 90 min 200 mg 4–50 mg or 2–100 mg 60 mL 200 mL 260 mL 1.4 mL/min or 84 mL/ hour 180 min Pediatric Patients The volume of infusion solution required to deliver the dose is dependent on the weight of the child.

The reconstituted solution must be further diluted to a concentration of 0.77 mg/mL for the final infusion solution.

A programmable syringe or infusion pump is recommended.

The rate of infusion should not exceed 1.1 mg/minute (equivalent to 1.4 mL/minute or 84 mL/hour when reconstituted and diluted per instructions) .

Doses below 50 mg 1.

Calculate pediatric patient dose and aseptically reconstitute vial(s) required according to reconstitution instructions to provide a concentration of 3.33 mg/mL (if dose is 50 mg or above, see preparation instructions for Adult Patients above ) . 2.

Calculate the volume (mL) of reconstituted ERAXIS required: [ Volume of reconstituted ERAXIS (mL) = Dose of ERAXIS (mg) ÷ 3.33 mg/mL] 3.

Calculate the total volume of the infusion solution (mL) that contains a final concentration of 0.77 mg/mL: [ Total volume of infusion solution (mL) = Dose of ERAXIS (mg) ÷ 0.77 mg/mL] 4.

Calculate the volume of diluent [5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline)] required to prepare the infusion solution: [ Volume of diluent (mL) = Total volume of final infusion solution (mL) – Volume of reconstituted ERAXIS (mL)] 5.

Prepare the infusion solution by aseptically transferring the required volumes (mL) of the reconstituted ERAXIS and diluent [5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline)] into an infusion syringe or IV infusion bag needed for administration.

ERAXIS infusion solution can be stored at temperatures up to 25°C (77°F) for up to 48 hours.

Do not freeze.

Chemical and physical in-use stability of the infusion solution has been demonstrated for 48 hours at 25°C (77°F).

From a microbiological point of view, following good aseptic practices, the infusion solution can be utilized for up to 48 hours from preparation when stored at 25°C.

ERAXIS (anidulafungin) for Injection is supplied in a single-dose vial of sterile, lyophilized, preservative-free, white to off-white powder.

ERAXIS (anidulafungin) is available in the following packaging configuration: Single-Dose Vial of ERAXIS 50 mg NDC 0049-0114-28 One.

• 50 mg vial Single-Dose Vial of ERAXIS 100 mg NDC 0049-0116-28 One.

• 100 mg vial 16.2 Storage ERAXIS vials ERAXIS (unreconstituted) vials should be stored in a refrigerator at 2°C – 8°C (36°F – 46°F).

Do not freeze.

Excursions for 96 hours up to 25°C (77°F) are permitted, and the vial can be returned to storage at 2°C – 8°C (36°F – 46°F).

Reconstituted solution

ERAXIS reconstituted solution can be stored at up to 25°C (77°F) for up to 24 hours.

ERAXIS infusion solution can be stored at temperatures up to 25°C (77°F) for up to 48 hours.

Storage ERAXIS vials

ERAXIS (unreconstituted) vials should be stored in a refrigerator at 2°C – 8°C (36°F – 46°F).

Do not freeze.

Excursions for 96 hours up to 25°C (77°F) are permitted, and the vial can be returned to storage at 2°C – 8°C (36°F – 46°F).

Reconstituted solution

ERAXIS reconstituted solution can be stored at up to 25°C (77°F) for up to 24 hours.

ERAXIS infusion solution can be stored at temperatures up to 25°C (77°F) for up to 48 hours.

Based on findings from animal studies, ERAXIS can cause fetal harm when administered to a pregnant woman.

There are no available human data on the use of ERAXIS in pregnant women to inform a drug-associated risk of adverse developmental outcomes.

In animal reproduction studies fetal toxicity was observed in the presence of maternal toxicity when anidulafungin was administered to pregnant rabbits during organogenesis at 4 times the proposed therapeutic maintenance dose of 100 mg/day on the basis of relative body surface area.

Inform pregnant woman of the risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and to 20% respectively.

In a combined fertility and embryo-fetal development study in rats dosed with anidulafungin for 4 weeks prior to cohabitation and through cohabitation for males or for 2 weeks prior to cohabitation and continuing through gestation day for females, there was no maternal or embryo-fetal toxicity at intravenous doses up to 20 mg/kg/day (equivalent to 2 times the proposed therapeutic maintenance dose of 100 mg/day on the basis of relative body surface area).

In a rabbit embryo-fetal development study, intravenous administration of anidulafungin (0, 5, 10, and 20 mg/kg/day) from gestation day 7 through 19, resulted in reduced fetal weights and incomplete ossification in the presence of maternal toxicity (decreased body weight gain) at 20 mg/kg/day (equivalent to 4 times the proposed therapeutic maintenance dose of 100 mg/day on the basis of relative body surface area).

In a pre.

• and postnatal development study, pregnant rats were intravenously administered anidulafungin at doses of 2, 6, or 20 mg/kg/day from gestation day 7 through lactation day 20.

Maternal toxicity was observed at ≥6 mg/kg/day (clinical signs at ≥6 mg/kg/day and reduced body weight gain and food consumption during gestation at 20 mg/kg/day group).

There were no effects on the viability or growth and development of the offspring.

In this study, anidulafungin was detected in fetal plasma, indicating that it crossed the placental barrier.

The safety and effectiveness of

ERAXIS for the treatment of candidemia and the following Candida infections: intra-abdominal abscess and peritonitis, have been established in pediatric patients 1 month of age and older.

Use of

ERAXIS for this indication in this is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic, safety data in pediatric patients 1 month of age and older.

ERAXIS in patients younger than 1 month of age with candidemia/invasive candidiasis has not been established.

Candidemia/invasive candidiasis in pediatric patients younger than 1 month of age has a higher rate of central nervous system (CNS) and multi-organ dissemination than in older patients.

In addition, in patients younger than 1 month of age ERAXIS carries a potential risk of life-threatening toxicity associated with high doses of polysorbate 80, an inactive ingredient in ERAXIS.

ERAXIS in pediatric patients with esophageal candidiasis has not been established.

ERAXIS is contraindicated in adult and pediatric patients with HFI.

Because a diagnosis of

HFI may not yet be established in pediatric patients, obtain a careful history of HFI symptoms with fructose/sucrose exposure prior to administration of ERAXIS.

Of the total number of subjects (N = 197) in the pivotal clinical studies of anidulafungin, 35% were 65 years and over, while 18% were 75 years and over.

No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Dosage adjustments are not required for geriatric patients.