Micafungin (micafungin)

What is it used for?

Micafungin for Injection is indicated for: Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses in adult and pediatric patients 4 months of age and older . Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses without meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age . Treatment of Esophageal Candidiasis in adult and pediatric patients 4 months of age and older . Prophylaxis of Candida Infections in adult and pediatric patients 4 months of age and older undergoing hematopoietic stem cell transplantation . Limitations of Use The safety and effectiveness of Micafungin for Injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age as a higher dose may be needed . Micafungin for Injection has not been adequately studied in patients with endocarditis, osteomyelitis and meningoencephalitis due to Candida . The efficacy of Micafungin for Injection against infections caused by fungi other than Candida has not been established. Micafungin for Injection is an echinocandin indicated in adult and pediatric patients for: Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses in adult and pediatric patients 4 months of age and older. Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses without meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age.

Treatment of Esophageal Candidiasis in adult and pediatric patients 4 months of age and older. Prophylaxis of Candida Infections in adult and pediatric patients 4 months of age and older undergoing Hematopoietic Stem Cell Transplantation (HSCT). Limitations of Use The safety and effectiveness of Micafungin for Injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age as a higher dose may be needed. (1, 2.3, 8.4) Micafungin for Injection has not been adequately studied in patients with endocarditis, osteomyelitis or meningoencephalitis due to Candida . The efficacy of Micafungin for Injection against infections caused by fungi other than Candida has not been established.

How to take it

Recommended Dosage Administered by Indication, Weight and Age (2.1, 2.2, 2.3, 8.4) Adult Pediatric Patients 4 Months and Older 30 kg or less Pediatric Patients 4 Months and Older greater than 30 kg Pediatric Patients Younger than 4 Months of Age Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses 100 mg daily 2 mg/kg/day (maximum 100 mg daily) See below Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses without Meningoencephalitis and/or Ocular Dissemination See above See above 4 mg/kg/day Treatment of Esophageal Candidiasis 150 mg daily 3 mg/kg/day 2.5 mg/kg/day (maximum 150 mg daily) Not approved Prophylaxis of Candida Infections in HSCT Recipients 50 mg daily 1 mg/kg/day (maximum 50 mg daily) Not approved Infuse over 1 hour. See Full Prescribing Information for intravenous (IV) preparation and administration instructions.

Dosage for Adults The

recommended dosage for adult patients based on indications are shown in Table 1. Table 1. Micafungin for Injection Dosage in Adult Patients Indication Recommended Reconstituted Dose Once Daily Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses * 100 mg Treatment of Esophageal Candidiasis † 150 mg Prophylaxis of Candida Infections in HSCT Recipients ‡ 50 mg *In patients treated successfully for candidemia and other Candida infections, the mean duration of treatment was 15 days (range 10 to 47 days). † In patients treated successfully for esophageal candidiasis, the mean duration of treatment was 15 days (range 10 to 30 days). ‡ In hematopoietic stem cell transplant (HSCT) recipients who experienced success of prophylactic therapy, the mean duration of prophylaxis was 19 days (range 6 to 51 days).

Dosage for Pediatric Patients

4 Months and Older The recommended dosage for pediatric patients 4 months of age and older based on indication and weight are shown in Table 2. Table 2. Micafungin for Injection Dosage in Pediatric Patients (4 Months of Age and Older) Indication Dosage for Pediatric Patients 4 Months of Age and Older 30 kg or less Greater than 30 kg Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses 2 mg/kg once daily (maximum daily dose 100 mg) Treatment of Esophageal Candidiasis 3 mg/kg once daily 2.5 mg/kg once daily (maximum daily dose 150 mg) Prophylaxis of Candida Infections in HSCT Recipients 1 mg/kg once daily (maximum daily dose 50 mg)

Dosage for Pediatric Patients Younger

than 4 Months of Age Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses without meningoencephalitis and/or ocular dissemination The recommended dosage is 4 mg/kg once daily. The safety and effectiveness of micafungin for injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age as a higher dose may be needed .

Directions for Reconstitution, Dilution, and Preparation Do

not mix or co-infuse micafungin for injection with other medications. Micafungin for injection has been shown to precipitate when mixed directly with a number of other commonly used medications. Please read this entire section carefully before beginning reconstitution. Reconstitution Reconstitute micafungin for injection vials by aseptically adding 5 mL of one of the following compatible solutions: 0.9% Sodium Chloride Injection, USP (without a bacteriostatic agent) 5% Dextrose Injection, USP To minimize excessive foaming, gently dissolve the micafungin for injection powder by swirling the vial.

Do not vigorously shake the vial. Visually inspect the vial for particulate matter. Micafungin for injection 50 mg vial: after reconstitution each mL contains 10 mg of micafungin. Micafungin for injection 100 mg vial: after reconstitution each mL contains 20 mg of micafungin. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use if there is any evidence of precipitation or foreign matter. Aseptic technique must be strictly observed in all handling since no preservative or bacteriostatic agent is present in micafungin for injection or in the materials specified for reconstitution and dilution. The reconstituted product should be protected from light and may be stored in the original vial for up to 24 hours at room temperature, 25˚C (77˚F).

Dilution and Preparation The diluted solution should be protected from light. It is not necessary to cover the infusion drip chamber or the tubing. Adult Patients: Add the appropriate volume of reconstituted micafungin for injection into 100 mL of 0.9% Sodium Chloride Injection, USP or 100 mL of 5% Dextrose Injection, USP. Appropriately label the bag.

Pediatric Patients Calculate the total micafungin for injection dose in milligrams (mg) by multiplying the recommended pediatric dose (mg/kg) for a given indication and the weight of the patient in kilograms (kg). To calculate the volume (mL) of drug needed, divide the calculated dose (mg) from step 1 by the final concentration of the selected reconstituted vial(s) (either 10 mg/mL for the 50 mg vial or 20 mg/mL for the 100 mg vial), see example below: Using 50 mg vials: Divide the calculated mg dose (from step 1) by 10 mg/mL to determine the volume (mL) needed. OR Using 100 mg vials: Divide the calculated mg dose (from step 1) by 20 mg/mL to determine the volume (mL) needed.

Withdraw the calculated volume (mL) of drug needed from the selected concentration and size of reconstituted micafungin for injection vial(s) used in Step 2 (ensure the selected concentration and vial size used to calculate the dose is also used to prepare the infusion). Add the withdrawn volume of drug (step 3) to a 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP intravenous infusion bag or syringe. Ensure that the final concentration of the solution is between 0.5 mg/mL to 4 mg/mL. To decrease the risk of infusion reactions, concentrations above 1.5 mg/mL should be administered via central catheter . Appropriately label the infusion bag or syringe.

For concentrations above 1.5 mg/mL, if required, label to specifically warn to administer the solution via central catheter. The diluted infusion bag should be protected from light and may be stored for up to 24 hours at room temperature, 25˚C (77˚F). Micafungin for injection is preservative-free.

Discard partially used vials.

Infusion Volume and Duration Administer

micafungin for injection by intravenous infusion only. Infuse over one hour. More rapid infusions may result in more frequent histamine-mediated reactions . Flush an existing intravenous line with 0.9% Sodium Chloride Injection, USP, prior to infusion of micafungin for injection.

Pediatric Patients Micafungin for injection should be infused over one hour. To decrease the risk of infusion reactions, concentrations above 1.5 mg/mL should be administered via central catheter .

Dosage for Adults The

recommended dosage for adult patients based on indications are shown in Table 1. Table 1. Micafungin for Injection Dosage in Adult Patients Indication Recommended Reconstituted Dose Once Daily Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses * 100 mg Treatment of Esophageal Candidiasis † 150 mg Prophylaxis of Candida Infections in HSCT Recipients ‡ 50 mg *In patients treated successfully for candidemia and other Candida infections, the mean duration of treatment was 15 days (range 10 to 47 days). † In patients treated successfully for esophageal candidiasis, the mean duration of treatment was 15 days (range 10 to 30 days). ‡ In hematopoietic stem cell transplant (HSCT) recipients who experienced success of prophylactic therapy, the mean duration of prophylaxis was 19 days (range 6 to 51 days).

Dosage for Pediatric Patients

4 Months and Older The recommended dosage for pediatric patients 4 months of age and older based on indication and weight are shown in Table 2. Table 2. Micafungin for Injection Dosage in Pediatric Patients (4 Months of Age and Older) Indication Dosage for Pediatric Patients 4 Months of Age and Older 30 kg or less Greater than 30 kg Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses 2 mg/kg once daily (maximum daily dose 100 mg) Treatment of Esophageal Candidiasis 3 mg/kg once daily 2.5 mg/kg once daily (maximum daily dose 150 mg) Prophylaxis of Candida Infections in HSCT Recipients 1 mg/kg once daily (maximum daily dose 50 mg)

Dosage for Pediatric Patients Younger

than 4 Months of Age Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses without meningoencephalitis and/or ocular dissemination The recommended dosage is 4 mg/kg once daily. The safety and effectiveness of micafungin for injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age as a higher dose may be needed .

Directions for Reconstitution, Dilution, and Preparation Do

not mix or co-infuse micafungin for injection with other medications. Micafungin for injection has been shown to precipitate when mixed directly with a number of other commonly used medications. Please read this entire section carefully before beginning reconstitution. Reconstitution Reconstitute micafungin for injection vials by aseptically adding 5 mL of one of the following compatible solutions: 0.9% Sodium Chloride Injection, USP (without a bacteriostatic agent) 5% Dextrose Injection, USP To minimize excessive foaming, gently dissolve the micafungin for injection powder by swirling the vial.

Do not vigorously shake the vial. Visually inspect the vial for particulate matter. Micafungin for injection 50 mg vial: after reconstitution each mL contains 10 mg of micafungin. Micafungin for injection 100 mg vial: after reconstitution each mL contains 20 mg of micafungin. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use if there is any evidence of precipitation or foreign matter. Aseptic technique must be strictly observed in all handling since no preservative or bacteriostatic agent is present in micafungin for injection or in the materials specified for reconstitution and dilution. The reconstituted product should be protected from light and may be stored in the original vial for up to 24 hours at room temperature, 25˚C (77˚F).

Dilution and Preparation The diluted solution should be protected from light. It is not necessary to cover the infusion drip chamber or the tubing. Adult Patients: Add the appropriate volume of reconstituted micafungin for injection into 100 mL of 0.9% Sodium Chloride Injection, USP or 100 mL of 5% Dextrose Injection, USP. Appropriately label the bag.

Pediatric Patients Calculate the total micafungin for injection dose in milligrams (mg) by multiplying the recommended pediatric dose (mg/kg) for a given indication and the weight of the patient in kilograms (kg). To calculate the volume (mL) of drug needed, divide the calculated dose (mg) from step 1 by the final concentration of the selected reconstituted vial(s) (either 10 mg/mL for the 50 mg vial or 20 mg/mL for the 100 mg vial), see example below: Using 50 mg vials: Divide the calculated mg dose (from step 1) by 10 mg/mL to determine the volume (mL) needed. OR Using 100 mg vials: Divide the calculated mg dose (from step 1) by 20 mg/mL to determine the volume (mL) needed.

Withdraw the calculated volume (mL) of drug needed from the selected concentration and size of reconstituted micafungin for injection vial(s) used in Step 2 (ensure the selected concentration and vial size used to calculate the dose is also used to prepare the infusion). Add the withdrawn volume of drug (step 3) to a 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP intravenous infusion bag or syringe. Ensure that the final concentration of the solution is between 0.5 mg/mL to 4 mg/mL. To decrease the risk of infusion reactions, concentrations above 1.5 mg/mL should be administered via central catheter . Appropriately label the infusion bag or syringe.

For concentrations above 1.5 mg/mL, if required, label to specifically warn to administer the solution via central catheter. The diluted infusion bag should be protected from light and may be stored for up to 24 hours at room temperature, 25˚C (77˚F). Micafungin for injection is preservative-free.

Discard partially used vials.

Infusion Volume and Duration Administer

micafungin for injection by intravenous infusion only. Infuse over one hour. More rapid infusions may result in more frequent histamine-mediated reactions . Flush an existing intravenous line with 0.9% Sodium Chloride Injection, USP, prior to infusion of micafungin for injection.

Pediatric Patients Micafungin for injection should be infused over one hour. To decrease the risk of infusion reactions, concentrations above 1.5 mg/mL should be administered via central catheter .

Warnings

Hypersensitivity Reactions: Anaphylaxis and anaphylactoid reactions (including shock) have been observed. Discontinue micafungin for injection and administer appropriate treatment. Hematological Effects: Isolated cases of acute intravascular hemolysis, hemolytic anemia and hemoglobinuria have been reported. Monitor rate of hemolysis. Discontinue if severe. Hepatic Effects: Abnormalities in liver tests; isolated cases of hepatic impairment, hepatitis, and hepatic failure have been observed. Monitor hepatic function. Discontinue if severe dysfunction occurs. Renal Effects: Elevations in BUN and creatinine; isolated cases of renal impairment or acute renal failure have been reported. Monitor renal function. Infusion and Injection Site Reactions can occur including rash, pruritus, facial swelling, and vasodilatation. Monitor infusion closely, slow infusion rate if necessary. (2.5, 5.5)

Hypersensitivity Reactions Isolated

cases of serious hypersensitivity (anaphylaxis and anaphylactoid) reactions (including shock) have been reported in patients receiving micafungin for injection. If these reactions occur, micafungin for injection infusion should be discontinued and appropriate treatment administered.

Hematological Effects Acute

intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin for injection (200 mg) and oral prednisolone (20 mg). Cases of significant hemolysis and hemolytic anemia have also been reported in patients treated with micafungin for injection. Patients who develop clinical or laboratory evidence of hemolysis or hemolytic anemia during micafungin for injection therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/benefit of continuing micafungin for injection therapy.

Hepatic Effects Laboratory

abnormalities in liver function tests have been seen in healthy volunteers and patients treated with micafungin for injection. In some patients with serious underlying conditions who were receiving micafungin for injection along with multiple concomitant medications, clinical hepatic abnormalities have occurred, and isolated cases of significant hepatic impairment, hepatitis, and hepatic failure have been reported. Patients who develop abnormal liver function tests during micafungin for injection therapy should be monitored for evidence of worsening hepatic function and evaluated for the risk/benefit of continuing micafungin for injection therapy.

Renal Effects Elevations in

BUN and creatinine, and isolated cases of significant renal impairment or acute renal failure have been reported in patients who received micafungin for injection. In fluconazole-controlled trials, the incidence of drug-related renal adverse reactions was 0.4% for micafungin for injection-treated patients and 0.5% for fluconazole-treated patients. Patients who develop abnormal renal function tests during micafungin for injection therapy should be monitored for evidence of worsening renal function.

Infusion and Injection Site Reactions Possible

histamine-mediated symptoms have been reported with micafungin for injection, including rash, pruritus, facial swelling, and vasodilatation. Slow the infusion rate if infusion reaction occurs . Injection site reactions, including phlebitis and thrombophlebitis have been reported, at micafungin for injection doses of 50 to 150 mg/day. These reactions tended to occur more often in patients receiving micafungin for injection via peripheral intravenous administration .

Hypersensitivity Reactions Isolated

cases of serious hypersensitivity (anaphylaxis and anaphylactoid) reactions (including shock) have been reported in patients receiving micafungin for injection. If these reactions occur, micafungin for injection infusion should be discontinued and appropriate treatment administered.

Hematological Effects Acute

intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin for injection (200 mg) and oral prednisolone (20 mg). Cases of significant hemolysis and hemolytic anemia have also been reported in patients treated with micafungin for injection. Patients who develop clinical or laboratory evidence of hemolysis or hemolytic anemia during micafungin for injection therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/benefit of continuing micafungin for injection therapy.

Hepatic Effects Laboratory

abnormalities in liver function tests have been seen in healthy volunteers and patients treated with micafungin for injection. In some patients with serious underlying conditions who were receiving micafungin for injection along with multiple concomitant medications, clinical hepatic abnormalities have occurred, and isolated cases of significant hepatic impairment, hepatitis, and hepatic failure have been reported. Patients who develop abnormal liver function tests during micafungin for injection therapy should be monitored for evidence of worsening hepatic function and evaluated for the risk/benefit of continuing micafungin for injection therapy.

Renal Effects Elevations in

BUN and creatinine, and isolated cases of significant renal impairment or acute renal failure have been reported in patients who received micafungin for injection. In fluconazole-controlled trials, the incidence of drug-related renal adverse reactions was 0.4% for micafungin for injection-treated patients and 0.5% for fluconazole-treated patients. Patients who develop abnormal renal function tests during micafungin for injection therapy should be monitored for evidence of worsening renal function.

Infusion and Injection Site Reactions Possible

histamine-mediated symptoms have been reported with micafungin for injection, including rash, pruritus, facial swelling, and vasodilatation. Slow the infusion rate if infusion reaction occurs . Injection site reactions, including phlebitis and thrombophlebitis have been reported, at micafungin for injection doses of 50 to 150 mg/day. These reactions tended to occur more often in patients receiving micafungin for injection via peripheral intravenous administration .

Who should not take it

Micafungin for injection is contraindicated in persons with known hypersensitivity to micafungin, any component of micafungin for injection, or other echinocandins. Micafungin for injection is contraindicated in persons with known hypersensitivity to micafungin sodium, any component of micafungin for injection, or other echinocandins.

Pregnancy

Pregnancy Risk Summary Based on

findings from animal studies, micafungin for injection may cause fetal harm when administered to a pregnant woman . There is insufficient human data on the use of micafungin for injection in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, intravenous administration of micafungin sodium to pregnant rabbits during organogenesis at doses four times the maximum recommended human dose resulted in visceral abnormalities and increased abortion . Advise pregnant women of the risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations is 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 an embryo-fetal toxicity study in pregnant rabbits, intravenous administration of micafungin sodium during organogenesis (days 6 to 18 of gestation) resulted in fetal visceral abnormalities and abortion at 32 mg/kg, a dose equivalent to four times the recommended human dose based on body surface area comparisons.

Visceral abnormalities included abnormal lobation of the lung, levocardia, retrocaval ureter, anomalous right subclavian artery, and dilatation of the ureter.

Lactation Risk Summary There

are no data on the presence of micafungin in human milk, the effects on the breast-fed infant or the effects on milk production. Micafungin was present in the milk of lactating rats following intravenous administration. When a drug is present in animal milk, it is likely that the drug will be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for micafungin for injection, and any potential adverse effects on the breast-fed child from micafungin for injection, or from the underlying maternal condition.

Pediatric Use Pediatric Patients

4 Months of Age and Older The safety and effectiveness of micafungin for injection for the treatment of esophageal candidiasis, candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses, esophageal candidiasis, and for prophylaxis of Candida infections in patients undergoing HSCT have been established in pediatric patients 4 months of age and older. Use of micafungin for injection for these indications and in this age group is supported by evidence from adequate and well-controlled studies in adult and pediatric patients with additional pharmacokinetic and safety data in pediatric patients 4 months of age and older . Pediatric Patients Younger than 4 Months of Age Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses Without Meningoencephalitis and/or Ocular Dissemination in Pediatric Patients Younger Than 4 Months of Age The safety and effectiveness of micafungin for injection for the treatment of candidemia, acute disseminated candidiasis, Candida peritonitis and abscesses without meningoencephalitis and/or ocular dissemination at a dosage of 4 mg/kg once daily have been established in pediatric patients younger than 4 months of age. This use and dosage of micafungin for injection are supported by evidence from adequate and well-controlled studies in adult and pediatric patients 4 months of age and older with additional pharmacokinetic and safety data in pediatric patients younger than 4 months of age . Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses With Meningoencephalitis and/or Ocular Dissemination in Pediatric Patients Younger Than 4 Months of Age The safety and effectiveness of micafungin for injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age.

In a rabbit model of hematogenous Candida meningoencephalitis (HCME) with Candida albicans (minimum inhibitory concentration of 0.125 mcg/mL), a decrease in mean fungal burden in central nervous system (CNS) compartments assessed as the average of combined fungal burden in the cerebrum, cerebellum, and spinal cord relative to untreated controls, was observed with increasing micafungin dosages administered once daily for 7 days. Data from the rabbit model suggest that a micafungin dose regimen of 4 mg/kg once daily is inadequate to treat meningoencephalitis and that a dose regimen of approximately 10 to 25 mg/kg once daily may be necessary to lower fungal burden in the CNS in pediatric patients younger than 4 months of age . In this rabbit model, micafungin concentrations could not be reliably detected in cerebrospinal fluid (CSF). Due to limitations of the study design, the clinical significance of a decreased CNS fungal burden in the rabbit HCME model is uncertain.

A randomized controlled trial evaluated a micafungin for injection dose regimen of 10 mg/kg once daily in pediatric patients younger than 4 months of age with suspected or proven Candida meningoencephalitis. Fungal-free survival at 1 week after end of therapy was observed in 60% of micafungin for injection-treated vs. 70% of amphotericin B-treated patients, and all-cause mortality was 15% vs. 10%, respectively. However, because this study was terminated early and enrolled only 30 pediatric patients younger than 4 months of age (20 treated with micafungin for injection and 10 treated with amphotericin B) which was 13% of the planned enrollment for the study, no conclusions can be drawn regarding efficacy of micafungin for injection at this dose regimen.

In six uncontrolled, open-label studies, and a neonatal intensive care unit (ICU) medical records database, pediatric patients younger than 4 months of age with suspected Candida meningoencephalitis or disseminated candidemia received micafungin for injection at dose regimens ranging from 5 to 15 mg/kg once daily. Across the entire micafungin for injection development program, only 6 pediatric patients with proven Candida meningoencephalitis were treated with dosages of 2 mg/kg, 8 mg/kg and 10 mg/kg once daily. Micafungin was detected in the CSF of pediatric patients with suspected Candida meningoencephalitis.

No conclusions regarding the efficacy of a particular dosage of micafungin for injection or the penetration of micafungin into the CSF can be drawn due to limitations of the data, including but not limited to, multiple confounding factors, variable study designs, and limited numbers of patients. No new safety signals were observed with the use of micafungin for injection at dosages of 5 to 15 mg/kg once daily in pediatric patients younger than 4 months of age, and there was no discernible dose-response for adverse events. Although the dosage for the treatment of candidemia with meningoencephalitis has not been established, antifungal activity in various CNS compartments in the rabbit HCME model and limited clinical trial data suggest that in patients younger than 4 months of age, dose regimens 10 mg/kg once daily or higher may be necessary for the treatment of candidemia with meningoencephalitis.

Safety data from clinical studies for micafungin for injection at dose regimens of 10 to 15 mg/kg once daily in pediatric patients younger than 4 months of age did not reveal new safety signals. Treatment of Esophageal Candidiasis and Prophylaxis of Candida Infections in Patients Undergoing Hematopoietic Stem Cell Transplantation in Pediatric Patients Younger Than 4 Months of Age The safety and effectiveness of micafungin for injection in pediatric patients younger than 4 months of age have not been established for the: Treatment of esophageal candidiasis Prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation

Geriatric Use A

total of 418 subjects in clinical studies of micafungin for injection were 65 years of age and older, and 124 subjects were 75 years of age and older. No overall differences in safety and effectiveness were observed between these subjects and younger subjects. 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.

The exposure and disposition of a 50 mg micafungin for injection dose administered as a single 1-hour infusion to 10 healthy subjects aged 66 to 78 years were not significantly different from those in 10 healthy subjects aged 20 to 24 years. No dose adjustment is necessary for the elderly.

Use in Patients with Renal Impairment Micafungin

for injection does not require dose adjustment in patients with renal impairment. Supplementary dosing should not be required following hemodialysis .

Use in Patients with Hepatic Impairment Dose

adjustment of micafungin for injection is not required in patients with mild, moderate, or severe hepatic impairment .

Race and Gender No

dose adjustment of micafungin for injection is required based on gender or race. After 14 daily doses of 150 mg to healthy subjects, micafungin AUC in women was greater by approximately 23% compared with men, due to smaller body weight. No notable differences among white, black, and Hispanic subjects were seen.

The micafungin AUC was greater by 19% in Japanese subjects compared to blacks, due to smaller body weight. Pregnancy – Based on animal data, micafungin for injection may cause fetal harm. Advise pregnant women of the risk to the fetus. See 17 for PATIENT COUNSELING INFORMATION. Revised: 12/2025

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Hematological Effects Hepatic Effects Renal Effects Infusion and Injection Site Reactions Most common adverse reactions across adult and pediatric clinical trials for all indications include diarrhea, nausea, vomiting, abdominal pain, pyrexia, thrombocytopenia, neutropenia, and headache. In pediatric patients younger than 4 months of age, the following additional common adverse reactions were reported at an incidence rate of ≥15%: sepsis, acidosis, anemia, oxygen saturation decreased and hypokalemia. To report SUSPECTED ADVERSE REACTIONS, contact Hisun Pharmaceuticals USA, Inc. at 1-855-554-4786 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Clinical Trials Experience Because

clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of micafungin for injection cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. The overall safety of micafungin for injection was assessed in 520 healthy volunteers and 3417 adult and pediatric patients who received single or multiple doses of micafungin for injection across 50 clinical trials, including the invasive candidiasis, esophageal candidiasis and prophylaxis trials. The doses of micafungin for injection administered included doses above and below the recommended doses and ranged from 0.75 mg/kg to 15 mg/kg in pediatric patients and 12.5 mg to 150 mg/day or greater in adults.

Clinical Trials Experience in Adults In clinical trials with micafungin for injection, 2497/2748 (91%) adult patients experienced at least one adverse reaction. Candidemia and Other Candida Infections In a randomized, double-blind trial for the treatment of candidemia and other Candida infections, adverse reactions occurred in 183/200 (92%) and 171/193 (89%) patients in the micafungin for injection 100 mg/day, and caspofungin (70 mg loading dose followed by 50 mg/day dose) treatment groups, respectively. Selected adverse reactions occurring in 5% or more of the patients and more frequently in the micafungin for injection treatment group, are shown in Table 3.

Table 3. Selected * Adverse Reactions in Adult Patients with Candidemia and Other Candida Infections Adverse Reactions by System Organ Class † Micafungin for Injection 100 mg n (%) Caspofungin ‡ n (%) Number of Patients 200 193 Gastrointestinal Disorders 81 76 Diarrhea 15 14 Vomiting 18 16 Metabolism and Nutrition Disorders 77 73 Hypoglycemia 12 9 Hyperkalemia 10 5 General Disorders/Administration Site Conditions 59 51 Investigations 36 37 Blood Alkaline Phosphatase Increased 11 8 Cardiac Disorders 35 36 Atrial Fibrillation 5 0 Patient base: all randomized patients who received at least 1 dose of trial drug. * During IV treatment + 3 days. † Within a system organ class, patients may experience more than 1 adverse reaction. ‡ 70 mg loading dose on day 1 followed by 50 mg/day thereafter (caspofungin). In a second, supportive, randomized, double-blind trial for the treatment of candidemia and other Candida infections, adverse reactions occurred in 245/264 (93%) and 250/265 (94%) adult and pediatric patients in the micafungin for injection (100 mg/day) and amphotericin B liposome (3 mg/kg/day) treatment groups, respectively.

In this trial, the following adverse reactions were reported in patients at least 16 years of age in the micafungin for injection and amphotericin B liposome treatment groups, respectively: nausea (10% vs. 8%), diarrhea (11% vs. 11%), vomiting (13% vs. 9%), abnormal liver tests (4% vs. 3%), increased aspartate aminotransferase (3% vs. 2%), and increased blood alkaline phosphatase (3% vs. 2%). Esophageal Candidiasis In a randomized, double-blind study for treatment of esophageal candidiasis, a total of 202/260 (78%) patients who received micafungin for injection 150 mg/day and 186/258 (72%) patients who received intravenous fluconazole 200 mg/day experienced an adverse reaction. Adverse reactions resulting in discontinuation were reported in 17 (7%) micafungin for injection-treated patients; and in 12 (5%) fluconazole-treated patients.

Selected treatment-emergent adverse reactions occurring in 5% or more of the patients and more frequently in the micafungin for injection group, are shown in Table 4. Table 4. Selected * Adverse Reactions in Adult Patients with Esophageal Candidiasis Adverse Reactions by System Organ Class † Micafungin for Injection 150 mg/day n (%) Fluconazole 200 mg/day n (%) Number of Patients 260 258 Gastrointestinal Disorders 84 93 Diarrhea 27 29 Nausea 20 23 Vomiting 17 17 General Disorders/Administration Site Conditions 52 45 Pyrexia 34 21 Nervous System Disorders 42 40 Headache 22 20 Vascular Disorders 54 21 Phlebitis 49 13 Skin and Subcutaneous Tissue Disorders 36 26 Rash 14 6 Patient base: all randomized patients who received at least 1 dose of trial drug. * During treatment + 3 days. † Within a system organ class, patients may experience more than 1 adverse reaction.

Prophylaxis of Candida Infections in Hematopoietic Stem Cell Transplant Recipients A double-blind trial was conducted in a total of 882 patients scheduled to undergo an autologous or allogeneic hematopoietic stem cell transplant. The median duration of treatment was 18 days (range 1 to 51 days) in both treatment arms. All adult patients who received micafungin for injection or fluconazole experienced at least one adverse reaction during the study.

Treatment-emergent adverse reactions resulting in micafungin for injection discontinuation were reported in 15 (4%) adult patients; while those resulting in fluconazole discontinuation were reported in 32 (8%). Selected adverse reactions reported in 15% or more of adult patients and more frequently in the micafungin for injection treatment arm, are shown in Table 5. Table 5.

Selected Adverse Reactions in Adult Patients During Prophylaxis of Candida Infection in Hematopoietic Stem Cell Transplant Recipients System Organ Class Micafungin for Injection 50 mg/day n (%) Fluconazole 400 mg/day n (%) Number of Patients 382 409 Gastrointestinal Disorders 377 404 Diarrhea 294 327 Nausea 270 290 Vomiting 252 274 Abdominal Pain 100 93 Blood and Lymphatic System Disorders 368 385 Neutropenia 288 297 Thrombocytopenia 286 280 Skin and Subcutaneous Tissue Disorders 257 275 Rash 95 91 Nervous System Disorders 250 254 Headache 169 154 Psychiatric Disorders 233 235 Insomnia 142 140 Anxiety 84 87 Cardiac Disorders 133 138 Tachycardia 99 91 Patient base: all randomized adult patients who received at least 1 dose of trial drug. Other selected adverse reactions reported at less than 5% in adult clinical trials are listed below: Blood and lymphatic system disorders: coagulopathy, pancytopenia, thrombotic thrombocytopenic purpura Cardiac disorders: cardiac arrest, myocardial infarction, pericardial effusion General disorders and administration site conditions: infusion reaction, injection site thrombosis Hepatobiliary disorders: hepatocellular damage, hepatomegaly, jaundice, hepatic failure Immune disorders: hypersensitivity, anaphylactic reaction Metabolism and nutrition disorders: hypernatremia, hypokalemia Nervous system disorders: convulsions, encephalopathy, intracranial hemorrhage Psychiatric disorders: delirium Skin and subcutaneous tissue disorders: urticaria Clinical Trials Experience in Pediatric Patients The safety of micafungin for injection was assessed in 593 pediatric patients, 425 of whom were 4 months through 16 years of age and 168 of whom were 3 days to less than 4 months of age who received at least one dose of micafungin for injection across 15 clinical trials. Of the 425 pediatric patients, 4 months through 16 years of age enrolled in 11 clinical trials, 235 (55%) were male, 290 (68%) were white, with the following age distribution: 62 (15%) 4 months to <2 years, 108 (25%) 2 to 5 years, 140 (33%) 6 to 11 years, and 115 (27%) 12 to 16 years of age.

The mean treatment duration was 26.1 days. A total of 246 patients received at least one dose of micafungin for injection ranging from 2 to 10 mg/kg. Overall, 388/425 (91%) patients experienced at least one adverse reaction. Adverse reactions occurring in ≥15% or more of micafungin-treated pediatric patients 4 months of age and older are: vomiting (32%), diarrhea (24%), pyrexia (24%), hypokalemia (22%), nausea (21%), mucosal inflammation (19%), thrombocytopenia (19%), abdominal pain (18%), headache (15%), and hypertension (15%).

Two randomized, double-blind active-controlled trials included pediatric patients. In the invasive candidiasis/candidemia trial, the efficacy and safety of micafungin for injection (2 mg/kg/day for patients weighing 40 kg or less and 100 mg/day for patients weighing greater than 40 kg) was compared to amphotericin B liposome (3 mg/kg/day) in 112 pediatric patients. Treatment-emergent adverse reactions occurred in 51/56 (91%) of patients in the micafungin for injection group and 52/56 (93%) of patients in the amphotericin B liposome group.

Treatment-emergent adverse reactions resulting in drug discontinuation were reported in 2 (4%) micafungin for injection-treated pediatric patients and in 9 (16%) amphotericin B liposome-treated pediatric patients. The prophylaxis study in patients undergoing HSCT investigated the efficacy of micafungin for injection (1 mg/kg/day for patients weighing 50 kg or less and 50 mg/day for patients weighing greater than 50 kg) as compared to fluconazole (8 mg/kg/day for patients weighing 50 kg or less and 400 mg/day for patients weighing greater than 50 kg). All 91 pediatric patients experienced at least one treatment-emergent adverse reaction.

Three (7%) pediatric patients discontinued micafungin for injection due to adverse reaction, while one (2%) patient discontinued fluconazole. Selected adverse reactions, occurring in 15% or more of the patients and more frequently in a micafungin for injection group, for the two comparative trials are shown in Table 6. Table 6.

Selected Adverse Reactions in Pediatric Patients with Candidemia and Other Candida Infections (C/IC), and in Hematopoietic Stem-Cell Recipients During Prophylaxis of Candida Infections Adverse Reactions * C/IC † Prophylaxis Micafungin for Injection n = 56 n (%) Amphotericin B liposome n = 56 n (%) Micafungin for Injection n = 43 n (%) Fluconazole n = 48 n (%) Gastrointestinal disorders 22 18 43 45 Vomiting 10 8 28 32 Diarrhea 4 5 22 31 Nausea 4 4 30 25 Abdominal pain 2 2 15 12 Abdominal distension 1 1 8 6 General disorders and administration site conditions 14 14 41 46 Pyrexia 5 9 26 31 Infusion-related reaction 0 3 7 4 Skin and subcutaneous tissue disorders 11 8 33 38 Pruritus 0 1 14 15 Rash 1 1 13 13 Urticaria 0 1 8 4 Respiratory, thoracic and mediastinal disorders 9 13 30 33 Epistaxis 0 0 4 8 Blood and lymphatic system disorders 17 13 40 44 Thrombocytopenia 5 3 31 37 Neutropenia 3 4 33 34 Anemia 10 6 22 24 Febrile neutropenia 0 0 7 7 Investigations 12 8 24 25 Alanine aminotransferase increased 0 0 7 1 Urine output decreased 0 0 10 8 Cardiac disorders 7 3 10 17 Tachycardia 2 1 7 12 Renal and urinary disorders 4 4 16 15 Hematuria 0 0 10 7 Psychiatric disorders 3 1 20 9 Anxiety 0 0 10 3 * Within a system organ class, patients may experience more than 1 adverse reaction. † Study population included 20 pediatric patients younger than 4 months of age (10 in each arm) Other clinically significant adverse reactions reported at less than 15% in pediatric clinical trials are listed below: Hepatobiliary disorders: hyperbilirubinemia Investigations: liver tests abnormal Renal Disorders: renal failure Clinical Trials Experience in Pediatric Patients Younger than 4 Months of Age The safety of micafungin for injection was assessed in 168 pediatric patients younger than 4 months of age who received varying doses of micafungin for injection in 9 clinical trials. The mean treatment duration was 16.6 days. A total of 59 patients received micafungin for injection at doses ≤4 mg/kg/day and 109 patients received micafungin for injection doses >4 mg/kg/day [5 to 15 mg/kg/day (approximately 1.3 to 3.8 times the recommended dosage in pediatric patients less than 4 months old)].

The adverse reaction profile of micafungin for injection in pediatric patients younger than 4 months of age was generally comparable to that of pediatric patients 4 months of age and older and adults. The most frequent adverse reactions (≥15%) in pediatric patients younger than 4 months old receiving a micafungin for injection dose of approximately 4 mg/kg/day included hypokalemia (25%), thrombocytopenia (25%), acidosis (20%), sepsis (20%), anemia (15%), oxygen saturation decreased (15%), and vomiting (15%). No new safety signals were seen in patients who received 5 to 15 mg/kg/day . Additional clinically significant adverse reactions reported in less than 15% of pediatric patients younger than 4 months of age who received approximately 4 mg/kg/day are listed below: Blood and Lymphatic System Disorders: leukocytosis, thrombocytosis, coagulation disorder neonatal Gastrointestinal Disorders: hematochezia, intestinal perforation, ascites, ileus, intestinal infarction, diarrhea, abdominal distension General Disorders and Administration Site Conditions: peripheral swelling, generalized edema, pyrexia, infusion site extravasation, edema neonatal Hepatobiliary Disorders: hyperbilirubinemia Investigations: blood lactate dehydrogenase increased, blood urea increased, ECG QRS complex prolonged Vascular Disorders: neonatal hypotension, thrombophlebitis Musculoskeletal and connective tissue disorders: hypertonia neonatal Respiratory, thoracic and mediastinal disorders: pleural effusion, respiratory failure, neonatal aspiration, respiratory distress Metabolism and nutrition disorders: hyperglycemia, dehydration, hypocalcemia, hypermagnesemia

Postmarketing Experience The

following adverse reactions have been identified during post-approval use of micafungin for injection. 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. Blood and lymphatic system disorders: disseminated intravascular coagulation Hepatobiliary disorders: hepatic disorder Renal and urinary disorders: renal impairment Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis Vascular disorders: shock