Anidulafungin

ERAXIS for Injection is a sterile, lyophilized product for intravenous (IV) infusion that contains anidulafungin. ERAXIS (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. ERAXIS (anidulafungin) is 1-[(4R,5R)-4,5-dihydroxy-N 2 -[[4"-(pentyloxy)[1,1':4',1"-terphenyl]-4-yl]carbonyl]-L-ornithine]echinocandin B. Anidulafungin is a white to off-white powder that is practically insoluble in water and slightly soluble in ethanol. In addition to the active ingredient, anidulafungin, ERAXIS for Injection contains the following inactive ingredients: 50 mg/vial – fructose (50 mg), mannitol (250 mg), polysorbate 80 (125 mg), tartaric acid (5.6 mg), and sodium hydroxide and/or hydrochloric acid for pH adjustment. 100 mg/vial – fructose (100 mg), mannitol (500 mg), polysorbate 80 (250 mg), tartaric acid (11.2 mg), and sodium hydroxide and/or hydrochloric acid for pH adjustment. The empirical formula of anidulafungin is C 58 H 73 N 7 O 17 and the formula weight is 1140.3. The structural formula is: Prior to administration, ERAXIS for Injection requires reconstitution with sterile Water for Injection and subsequent dilution with either 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline). Chemical Structure

ERAXIS is an echinocandin antifungal indicated for the treatment of the following infections: • Candidemia and other forms of Candida infections (intra-abdominal abscess and peritonitis) in adults and pediatric patients (1 month of age and older) ( 1.1 ) • Esophageal candidiasis in adults ( 1.2 ) Limitations of use • ERAXIS has not been studied in adult and pediatric patients with endocarditis, osteomyelitis, and meningitis due to Candida or in sufficient numbers of neutropenic patients. The dosage of ERAXIS for the treatment of Candida dissemination into the CNS and the eye has not been established. ( 1.3 , 5.3 , 8.4 ) • ERAXIS is associated with high relapse rates in esophageal candidiasis. ( 1.3 , 14.2 ) 1.1 Candidemia and Other Forms of Candida Infections (Intra-abdominal Abscess and Peritonitis) ERAXIS is indicated for the treatment of candidemia and the following Candida infections: intra-abdominal abscess and peritonitis in adults and pediatric patients 1 month of age and older [see Clinical Studies (14.1) and Microbiology (12.4) ] . 1.2 Esophageal Candidiasis ERAXIS is indicated for the treatment of esophageal candidiasis in adults [see Indications and Usage (1.3) , Clinical Studies (14.2) ] . 1.3 Limitations of Use • ERAXIS has not been studied in adult and pediatric patients with endocarditis, osteomyelitis, and meningitis due to Candida, and has not been studied in sufficient numbers of neutropenic patients to determine efficacy in this group. The dosage of ERAXIS for the treatment of Candida dissemination into the CNS and the eye has not been established [see Warning and Precautions (5.3) , Use in Specific Populations (8.4) ]. • ERAXIS is associated with high relapse rates in esophageal candidiasis [see Clinical Studies (14.2) ]. 1.4 Usage Specimens for fungal culture and other relevant laboratory studies (including histopathology) should be obtained prior to therapy to isolate and identify causative organism(s). Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.

16.1 How Supplied 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 [see Dosage and Administration (2.3) ] . Infusion Solution ERAXIS infusion solution can be stored at temperatures up to 25°C (77°F) for up to 48 hours. Do not freeze [see Dosage and Administration (2.4) ] .

Adults Pediatric 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 ( 2.1 ) 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 ( 2.2 ) 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 ( 2.1 ) 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] ( 2.3 , 2.4 ) 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. Esophageal Candidiasis 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. Duration of treatment should be based on the patient's clinical response. 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. Storage of the Reconstituted Solution 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. Adult Patients 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). See Table 1 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) [see Warnings and Precautions (5.2) ]. 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) [see Warnings and Precautions (5.2) ] . Steps for the Preparation of Pediatric 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 ) [see Dosage and Administration (2.2 , 2.3) ] . 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. Storage of the Infusion Solution 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 is contraindicated in: • Patients with known hypersensitivity to anidulafungin, any component of ERAXIS, or other echinocandins [see Warnings and Precautions (5.2) ] • Patients with known or suspected Hereditary Fructose Intolerance (HFI) [see Warnings and Precautions (5.4) ] • Known hypersensitivity to anidulafungin, any component of ERAXIS, or other echinocandins ( 4 , 5.2 ) • Known or suspected Hereditary Fructose Intolerance (HFI) ( 4 , 5.4 )

Hepatic Adverse Reactions Inform patients about the risk of developing abnormal liver function tests and/or hepatic dysfunction. Advise the patient that liver function tests may be monitored during treatment. Anaphylactic and Hypersensitivity Reactions Inform the patient that anaphylactic reactions, including shock were reported with ERAXIS. Inform the patient if these reactions occur, ERAXIS may be discontinued and appropriate treatment administered. Inform the patient that ERAXIS is also known to cause infusion-related adverse reactions, possibly histamine-mediated. Inform the patient to report symptoms including rash, urticaria, flushing, pruritus, dyspnea, and hypotension to their healthcare provider. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk of ERAXIS to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy. Patients with Hereditary Fructose Intolerance (HFI) Inform patients and caregivers that ERAXIS contains fructose and can be life-threatening when administered to patients with hereditary fructose intolerance (HFI) [see Warnings and Precautions (5.4) ] . Inquire for symptoms of fructose and/or sucrose intolerance.

7.1 Cyclosporine Administration of multiple doses of anidulafungin and cyclosporine to healthy subjects resulted in no significant alteration in the steady state pharmacokinetics of either drug. No dosage adjustment of cyclosporine or anidulafungin is needed when the two drugs are co-administered [see Clinical Pharmacology (12.3) ] . 7.2 Voriconazole Administration of multiple doses of anidulafungin and voriconazole to healthy subjects resulted in no significant alteration in the steady state pharmacokinetics of either drug. No dosage adjustment of voriconazole or anidulafungin is needed when the two drugs are co-administered [see Clinical Pharmacology (12.3) ] . 7.3 Tacrolimus Administration of multiple doses of anidulafungin and a single-dose of tacrolimus to healthy subjects resulted in no significant alteration in the steady state pharmacokinetics of either drug. No dosage adjustment of tacrolimus or anidulafungin is needed when the two drugs are co-administered [see Clinical Pharmacology (12.3) ] . 7.4 Rifampin Administration of multiple doses of anidulafungin and rifampin to patients resulted in no significant alteration in the steady state pharmacokinetics of anidulafungin. No dosage adjustment of anidulafungin is needed when it is co-administered with rifampin [see Clinical Pharmacology (12.3) ] . 7.5 Amphotericin B Liposome for Injection Administration of multiple doses of anidulafungin and liposomal amphotericin B to patients resulted in no significant alteration in the steady state pharmacokinetics of anidulafungin. No dosage adjustment of anidulafungin is needed when it is co-administered with liposomal amphotericin B [see Clinical Pharmacology (12.3) ] .

Long-term animal carcinogenicity studies of anidulafungin have not been conducted. Anidulafungin was not genotoxic in the following in vitro studies: bacterial reverse mutation assays, a chromosome aberration assay with Chinese hamster ovary cells, and a forward gene mutation assay with mouse lymphoma cells. Anidulafungin was not genotoxic in mice using the in vivo micronucleus assay. Anidulafungin produced no adverse effects on fertility in male or female rats at intravenous doses of 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).

Risk Summary 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 ( see Data ) . 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 2 to 4% and 15 to 20% respectively. Data Animal Data 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 19 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 age group 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 [see Indications and Usage (1) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ]. The safety and effectiveness of 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 [see Warnings and Precautions (5.3) ] . The safety and effectiveness of 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 [see Warnings and Precautions (5.4) ] .

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 [see Clinical Pharmacology (12.3) ] .

The following most serious adverse reactions are described elsewhere in other labeling sections: • Hepatic Adverse Reactions [see Warnings and Precautions (5.1) ] • Anaphylactic and Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Adults • Candidemia and other forms of Candida infections: Most common adverse reactions (≥15%) are hypokalemia, nausea, diarrhea, vomiting, pyrexia, insomnia, hypotension. ( 6.1 ) • Esophageal candidiasis: Most common adverse reactions (≥5%) are diarrhea, pyrexia, anemia, headache, vomiting, nausea, dyspepsia, oral candidiasis, and hypokalemia. ( 6.1 ) Pediatric Patients (1 month and older) Candidemia and other forms of Candida infections: Most common adverse reactions (≥ 5%): diarrhea, vomiting, pyrexia, abdominal pain, anemia, thrombocytopenia, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased, hypoglycemia, epistaxis, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials Experience in Adults The safety of ERAXIS for Injection was assessed in 929 individuals, including 257 healthy subjects and 672 patients in clinical trials of candidemia, other forms of Candida infections, and esophageal candidiasis. A total of 633 patients received ERAXIS at daily doses of either 50 mg or 100 mg. A total of 481 patients received ERAXIS for ≥14 days. Candidemia/other Candida Infections Three trials (one comparative vs. fluconazole, two non-comparative) assessed the efficacy and safety of ERAXIS (100 mg) in patients with candidemia and other Candida infections. The data described below reflect exposure to ERAXIS and fluconazole in 127 and 118 patients, respectively, with candidemia and other forms of invasive candidiasis, in the randomized, comparative trial of the efficacy and safety of ERAXIS to that of fluconazole. In ERAXIS-treated patients, the age range was 16–89 years, the gender distribution was 51% male and 49% female, and the race distribution was 72% White, 18% Black/African American, 9% other races. Patients were randomized to receive once daily IV ERAXIS (200 mg loading dose followed by 100 mg maintenance dose) or IV fluconazole (800 mg loading dose followed by 400 mg maintenance dose). Treatment was administered for at least 14 and not more than 42 days. The number of patients with adverse reactions leading to discontinuation of study medication was 11.5% in the ERAXIS arm and 21.6% in the fluconazole arm. The most common adverse reactions leading to study drug discontinuation were multi-organ failure (2.3%) and systemic Candida infection (1.5%) in the ERAXIS arm. Table 2 presents adverse reactions that were reported in ≥5% of subjects receiving ERAXIS or fluconazole therapy in this trial. Table 2: Adverse Reactions Reported in ≥5% of Adult Patients Receiving ERAXIS or Fluconazole Therapy for Candidemia/other Candida Infections A patient who experienced multiple reactions within a Body System or preferred term was counted one time for that class, one time for the preferred term and one time for "subjects with at least one adverse reaction". , This trial was not designed to support comparative claims for ERAXIS for the adverse reactions reported in this table. Adverse Reaction ERAXIS 100 mg N=131 Fluconazole 400 mg N=125 N (%) N (%) Subjects with a least one adverse reaction 130 (99) 122 (98) Gastrointestinal disorders 81 (62) 72 (58) Nausea 32 (24) 15 (12) Diarrhea 24 (18) 23 (18) Vomiting 23 (18) 12 (10) Constipation 11 (8) 14 (11) Abdominal pain 8 (6) 16 (13) General disorders and administration site conditions 70 (53) 76 (61) Pyrexia 23 (18) 23 (18) Edema peripheral 14 (11) 16 (13) Chest pain 7 (5) 6 (5) Respiratory, thoracic, and mediastinal disorders 67 (51) 55 (44) Dyspnea 15 (12) 4 (3) Pleural effusion 13 (10) 11 (9) Cough 9 (7) 7 (6) Respiratory distress 8 (6) 2 (2) Investigations 66 (50) 46 (37) Blood alkaline phosphatase increased 15 (12) 14 (11) White blood cell increased 11 (8) 3 (2) Hepatic enzyme increased 7 (5) 14 (11) Blood creatinine increased 7 (5) 1 (1) Metabolism and nutrition disorders 61 (47) 61 (49) Hypokalemia 33 (25) 24 (19) Hypomagnesemia 15 (12) 14 (11) Hypoglycemia 9 (7) 10 (8) Hyperkalemia 8 (6) 14 (11) Hyperglycemia 8 (6) 8 (6) Dehydration 8 (6) 2 (2) Vascular disorders 50 (38) 41 (33) Hypotension 19 (15) 18 (14) Hypertension 15 (12) 5 (4) Deep vein thrombosis 13 (10) 9 (7) Psychiatric disorders 48 (37) 45 (36) Insomnia 20 (15) 12 (10) Confusional state 10 (8) 10 (8) Depression 8 (6) 5 (4) Blood and lymphatic system disorders 34 (26) 36 (29) Anemia 12 (9) 20 (16) Thrombocythemia 8 (6) 1 (1) Leukocytosis 7 (5) 6 (5) Skin and subcutaneous tissue disorders 30 (23) 32 (26) Decubitus ulcer 7 (5) 10 (8) Nervous system disorders 27 (21) 31 (25) Headache 11 (8) 10 (8) Musculoskeletal and connective tissue disorders 27 (21) 25 (20) Back pain 7 (5) 13 (10) Esophageal Candidiasis The data described below reflect exposure to ERAXIS and fluconazole in 300 and 301 patients, respectively, with esophageal candidiasis in a randomized trial comparing the efficacy and safety of ERAXIS to that of oral fluconazole. In ERAXIS-treated patients, the age range was 18–68 years, the gender distribution was 42% male and 58% female and the race distribution was 15% White, 49% Black/African American, 15% Asian, 0.3 % Hispanic, 21% other races. Patients were randomized to receive IV ERAXIS (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14–21 days). Twenty-eight (9%) patients in the ERAXIS arm and 36 (12%) patients in the fluconazole arm had adverse reactions related to study medication. The most common adverse reactions leading to study discontinuation were maculopapular rash (1 patient) for the ERAXIS arm. The most common adverse reactions leading to discontinuation were rash (1 patient) and increased AST (1 patient) for the fluconazole arm. Table 3 presents adverse reactions that were reported in ≥5% of subjects receiving ERAXIS therapy. Table 3: Adverse Reactions Reported in ≥5% of Adult Patients Receiving ERAXIS or Fluconazole Therapy for Esophageal Candidiasis A patient who experienced multiple reactions within a Body System or preferred term was counted one time for that class, one time for the preferred term and one time for "subjects with at least one adverse reaction". , This trial was not designed to support comparative claims for ERAXIS for the adverse reactions reported in this table. Adverse Reaction ERAXIS 50 mg N=300 Fluconazole 100 mg N=301 N (%) N (%) Subjects with a least one adverse reaction 239 (80) 227 (75) Infections and infestations 115 (38) 99 (33) Oral candidiasis 15 (5) 10 (3) Gastrointestinal disorders 106 (35) 113 (38) Diarrhea 27 (9) 26 (9) Vomiting 27 (7) 30 (10) Nausea 20 (7) 23 (8) Dyspepsia 20 (7) 21 (7) Blood and lymphatic system disorders 55 (18) 50 (17) Anemia 25 (8) 22 (7) Metabolism and nutrition disorders 50 (17) 46 (15) Hypokalemia 14 (5) 17 (6) General disorders and administration site condition 49 (16) 54 (18) Pyrexia 27 (9) 28 (9) Nervous system disorders 39 (13) 36 (12) Headache 25 (8) 20 (7) Less Common Adverse Reactions in Adult Patients with Candidemia/other Candida Infections and Esophageal Candidiasis The following selected adverse reactions occurred in <2% of patients: Blood and Lymphatic : coagulopathy, thrombocytopenia Cardiac : atrial fibrillation, bundle branch block (right), sinus arrhythmia, ventricular extrasystoles Eye : eye pain, vision blurred, visual disturbance General and Administration Site : infusion related reaction, peripheral edema, rigors Hepatobiliary : abnormal liver function tests, cholestasis, hepatic necrosis Infections : clostridial infection Investigations : amylase increased, bilirubin increased, CPK increased, electrocardiogram QT prolonged, gamma-glutamyl transferase increased, lipase increased, potassium decreased, prothrombin time prolonged, urea increased Nervous System : convulsion, dizziness Respiratory, Thoracic and Mediastinal : cough Skin and Subcutaneous Tissue : angioneurotic edema, erythema, pruritus, sweating increased, urticaria Vascular : flushing, hot flushes, thrombophlebitis superficial Clinical Trials Experience in Pediatric Patients with Candidemia/Invasive Candidiasis The safety of ERAXIS was investigated in 68 pediatric patients from 1 month to less than 18 years of age with candidemia/invasive candidiasis in a prospective, open-label, non-comparative pediatric trial [see Clinical Studies (14.1) ] . Overall, the safety profile of ERAXIS in the pediatric patients 1 month and older was similar to that of adults. Most Common Adverse Reactions The most common adverse reactions occurring in ≥5% of pediatric patients receiving ERAXIS therapy in the clinical trial are displayed by body system in Table 4. Table 4Adverse Reactions Occurring in ≥5% of Pediatric Patients Receiving ERAXIS Therapy for Candidemia/other Candida Infections Reflects adverse reactions including those that started on or after first dose of anidulafungin through 6-week follow-up for patients who did not receive oral fluconazole, and those that started between first dose and last dose of anidulafungin for patients who received oral fluconazole. , A patient who experienced multiple reactions within a Body System or preferred term was counted one time for that class, one time for the preferred term and one time for "subjects with at least one adverse reaction". Adverse Reaction 1 month to <2 years N=19 2 to <5 years N=19 5 to <18 years N=30 Overall N=68 n (%) n (%) n (%) n (%) Subjects with a least one adverse reaction 17 (90) 14 (74) 24 (80) 55 (81) Blood and lymphatic system disorders 9 (47) 3 (16) 4 (13) 16 (24) Anemia 5 (26) 2 (11) 0 7 (10) Thrombocytopenia 2 (11) 1 (5) 1 (3) 4 (6) Gastrointestinal disorders 8 (42) 8 (42) 12 (40) 28 (41) Diarrhea 4 (21) 2 (11) 5 (17) 11 (16) Vomiting 4 (21) 5 (26) 2 (7) 11 (16) Abdominal pain Includes such terms as: abdominal pain and abdominal pain upper. 0 4 (21) 2 (7) 6 (9) General disorders and administration site condition 5 (26) 6 (32) 9 (30) 20 (29) Pyrexia 4 (21) 3 (16) 5 (17) 12 (18) Laboratory Investigations 4 (21) 4 (21) 8 (27) 16 (24) Alanine aminotransferase increased 2 (11) 2 (11) 2 (7) 6 (9) Aspartate aminotransferase increased 2 (11) 1 (5) 1 (3) 4 (6) Metabolism and nutrition disorders 3 (16) 4 (21) 6 (20) 13 (19) Hypoglycemia 1 (5) 2 (11) 1 (3) 4 (6) Respiratory, thoracic and mediastinal disorders 5 (26) 5 (26) 5 (17) 15 (22) Epistaxis 1 (5) 2 (11) 3 (10) 6 (9) Skin and subcutaneous tissue disorders 6 (32) 5 (26) 5 (17) 16 (24) Rash Includes such terms as: rash and rash generalized. 3 (16) 1 (5) 2 (7) 6 (9) Other adverse reactions were reported in 2 or more pediatric patients and in less than 5% of the 68 pediatric patients treated with ERAXIS in the clinical trial: Blood and Lymphatic System Disorders: pancytopenia, thrombocytosis, febrile neutropenia, leukopenia, neutropenia Eye Disorders: Periorbital edema Gastrointestinal Disorders: gastroesophageal reflux disease, abdominal distension, nausea, stomatitis, dry mouth General Disorders and Administrative Site Conditions: chest pain, edema peripheral Infections and Infestations: bacteremia, device related infection, gastroenteritis, lower respiratory tract infection, upper respiratory tract infection, urinary tract infection Laboratory Investigations: gamma-glutamyltransferase increased, transaminases increased Metabolism and Nutrition Disorders: hypocalcemia, hypokalemia, hyponatremia, hypoproteinemia Musculoskeletal and Connective Tissue Disorders: back pain, pain in extremity Nervous System Disorders: headache, tremor, seizure Psychiatric Disorders: agitation Respiratory, Thoracic and Mediastinal Disorders: hemoptysis Vascular Disorders: hypotension 6.2 Post-marketing Experience The following adverse reactions have been identified during post approval use of anidulafungin. 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. Immune : Anaphylactic shock, anaphylactic reaction, bronchospasm [see Warnings and Precautions (5.2) ] .

During clinical trials a single 400 mg dose of ERAXIS was inadvertently administered as a loading dose. No clinical adverse events were reported. In a study of 10 healthy subjects administered a loading dose of 260 mg followed by 130 mg daily; 3 of the 10 subjects experienced transient, asymptomatic transaminase elevations (≤3 × ULN) [see Warnings and Precautions (5.1) ] . Anidulafungin is not dialyzable. 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) or equivalent to 5 times the recommended daily dose for candidemia and other Candida infections (100 mg/day), based on relative body surface area comparisons.