Mycamine

Micafungin sodium · Injection, Powder, Lyophilized, For Solution · Intravenous

Prescription (Rx) Echinocandin Antifungal 1 recall

Uses

1 INDICATIONS AND USAGE MYCAMINE ® is indicated for:
• Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses in adult and pediatric patients 4 months of age and older [see Clinical Studies ( 14.1 ) and Use in Specific Populations ( 8.4 )].
• 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 [see Use in Specific Populations ( 8.4 )] .
• Treatment of Esophageal Candidiasis in adult and pediatric patients 4 months of age and older [see Clinical Studies ( 14.2 )] .
• Prophylaxis of Candida Infections in adult and pediatric patients 4 months of age and older undergoing hematopoietic stem cell transplantation [see Clinical Studies ( 14.3 )] . Limitations of Use
• The safety and effectiveness of MYCAMINE 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 [see Use in Specific Populations ( 8.4 )] .
• MYCAMINE has not been adequately studied in patients with endocarditis, osteomyelitis and meningoencephalitis due to Candida .
• The efficacy of MYCAMINE against infections caused by fungi other than Candida has not been established. MYCAMINE ® is an echinocandin indicated in adult and pediatric patients for ( 1 ):
• 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 MYCAMINE 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 )
• MYCAMINE has not been adequately studied in patients with endocarditis, osteomyelitis or meningoencephalitis due to Candida. ( 1 )
• The efficacy of MYCAMINE against infections caused by fungi other than Candida has not been established. ( 1 )

Dosage and administration

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. ( 2.5 )
• See Full Prescribing Information for intravenous (IV) preparation and administration instructions. ( 2 ) 2.1 Dosage for Adults The recommended dosage for adult patients based on indications are shown in Table 1 . Table 1. MYCAMINE Dosage in Adult Patients Indication Recommended Reconstituted Dose Once Daily Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses In patients treated successfully for candidemia and other Candida infections, the mean duration of treatment was 15 days (range 10 to 47 days). 100 mg Treatment of Esophageal Candidiasis In patients treated successfully for esophageal candidiasis, the mean duration of treatment was 15 days (range 10 to 30 days). 150 mg Prophylaxis of Candida Infections in HSCT Recipients 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). 50 mg 2.2 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. MYCAMINE 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) 2.3 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 MYCAMINE 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 [see Use in Specific Populations ( 8.4 ), Clinical Pharmacology ( 12.3 ) and Microbiology ( 12.4 )] . 2.4 Directions for Reconstitution, Dilution, and Preparation Do not mix or co-infuse MYCAMINE with other medications. MYCAMINE 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 MYCAMINE 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 MYCAMINE powder by swirling the vial. Do not vigorously shake the vial . Visually inspect the vial for particulate matter. MYCAMINE 50 mg vial : after reconstitution each mL contains 10 mg of micafungin. MYCAMINE 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 MYCAMINE 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 o C (77 o 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: 1. Add the appropriate volume of reconstituted MYCAMINE into 100 mL of 0.9% Sodium Chloride Injection, USP or 100 mL of 5% Dextrose Injection, USP. 2. Appropriately label the bag. Pediatric Patients 1. Calculate the total MYCAMINE dose in milligrams (mg) by multiplying the recommended pediatric dose (mg/kg) for a given indication [see Table 2 ] and the weight of the patient in kilograms (kg). 2. 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. 3. Withdraw the calculated volume (mL) of drug needed from the selected concentration and size of reconstituted MYCAMINE 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). 4. 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.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS MYCAMINE is a sterile, white lyophilized powder for reconstitution for intravenous infusion available as:
• 50 mg single-dose vial
• 100 mg single-dose vial
• For injection: 50 mg single-dose vial. ( 3 )
• For injection: 100 mg single-dose vial. ( 3 )

Contraindications

4 CONTRAINDICATIONS MYCAMINE is contraindicated in persons with known hypersensitivity to micafungin, any component of MYCAMINE, or other echinocandins. MYCAMINE is contraindicated in persons with known hypersensitivity to micafungin sodium, any component of MYCAMINE, or other echinocandins. ( 4 )

Warnings and precautions

• Hypersensitivity Reactions: Anaphylaxis and anaphylactoid reactions (including shock) have been observed. Discontinue MYCAMINE and administer appropriate treatment. ( 5.1 )
• Hematological Effects: Isolated cases of acute intravascular hemolysis, hemolytic anemia and hemoglobinuria have been reported. Monitor rate of hemolysis. Discontinue if severe. ( 5.2 )
• 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. ( 5.3 )
• Renal Effects: Elevations in BUN and creatinine; isolated cases of renal impairment or acute renal failure have been reported. Monitor renal function. ( 5.4 )
• 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 ) 5.1 Hypersensitivity Reactions Isolated cases of serious hypersensitivity (anaphylaxis and anaphylactoid) reactions (including shock) have been reported in patients receiving MYCAMINE. If these reactions occur, MYCAMINE infusion should be discontinued and appropriate treatment administered. 5.2 Hematological Effects Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of MYCAMINE (200 mg) and oral prednisolone (20 mg). Cases of significant hemolysis and hemolytic anemia have also been reported in patients treated with MYCAMINE. Patients who develop clinical or laboratory evidence of hemolysis or hemolytic anemia during MYCAMINE therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/benefit of continuing MYCAMINE therapy. 5.3 Hepatic Effects Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with MYCAMINE. In some patients with serious underlying conditions who were receiving MYCAMINE 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 MYCAMINE therapy should be monitored for evidence of worsening hepatic function and evaluated for the risk/benefit of continuing MYCAMINE therapy. 5.4 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 MYCAMINE. In fluconazole-controlled trials, the incidence of drug-related renal adverse reactions was 0.4% for MYCAMINE-treated patients and 0.5% for fluconazole-treated patients. Patients who develop abnormal renal function tests during MYCAMINE therapy should be monitored for evidence of worsening renal function. 5.5 Infusion and Injection Site Reactions Possible histamine-mediated symptoms have been reported with MYCAMINE, including rash, pruritus, facial swelling, and vasodilatation. Slow the infusion rate if infusion reaction occurs [see Dosage and Administration ( 2.3 )]. Injection site reactions, including phlebitis and thrombophlebitis have been reported, at MYCAMINE doses of 50 to 150 mg/day. These reactions tended to occur more often in patients receiving MYCAMINE via peripheral intravenous administration [ see Dosage and Administration ( 2.3 ) and Adverse Reactions ( 6.1 )] .

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling:
• Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )]
• Hematological Effects [see Warnings and Precautions ( 5.2 )]
• Hepatic Effects [see Warnings and Precautions ( 5.3 )]
• Renal Effects [see Warnings and Precautions ( 5.4 )]
• Infusion and Injection Site Reactions [see Warnings and Precautions ( 5.5 )]
• Most common adverse reactions across adult and pediatric clinical trials for all indications include diarrhea, nausea, vomiting, abdominal pain, pyrexia, thrombocytopenia, neutropenia, and headache. ( 6.1 )
• 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 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 clinical trials of MYCAMINE 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 MYCAMINE was assessed in 520 healthy volunteers and 3417 adult and pediatric patients who received single or multiple doses of MYCAMINE across 50 clinical trials, including the invasive candidiasis, esophageal candidiasis and prophylaxis trials. The doses of MYCAMINE administered included doses above and below the recommended doses [see Dosage and Administration ( 2.1 , 2.2 )] 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 MYCAMINE, 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 MYCAMINE 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 MYCAMINE treatment group, are shown in Table 3 . Table 3. Selected During IV treatment + 3 days. Adverse Reactions in Adult Patients with Candidemia and Other Candida Infections Patient base: all randomized patients who received at least 1 dose of trial drug. Adverse Reactions by System Organ Class Within a system organ class, patients may experience more than 1 adverse reaction. MYCAMINE 100 mg n (%) Caspofungin 70 mg loading dose on day 1 followed by 50 mg/day thereafter (caspofungin). n (%) Number of Patients 200 193 Gastrointestinal Disorders 81 (41) 76 (39) Diarrhea 15 (8) 14 (7) Vomiting 18 (9) 16 (8) Metabolism and Nutrition Disorders 77 (39) 73 (38) Hypoglycemia 12 (6) 9 (5) Hyperkalemia 10 (5) 5 (3) General Disorders/Administration Site Conditions 59 (30) 51 (26) Investigations 36 (18) 37 (19) Blood Alkaline Phosphatase Increased 11 (6) 8 (4) Cardiac Disorders 35 (18) 36 (19) Atrial Fibrillation 5 (3) 0 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 MYCAMINE (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 MYCAMINE 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 MYCAMINE 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%) MYCAMINE-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 MYCAMINE group, are shown in Table 4 . Table 4. Selected During treatment + 3 days. Adverse Reactions in Adult Patients with Esophageal Candidiasis Patient base: all randomized patients who received at least 1 dose of trial drug. Adverse Reactions by System Organ Class Within a system organ class, patients may experience more than 1 adverse reaction. MYCAMINE 150 mg/day n (%) Fluconazole 200 mg/day n (%) Number of Patients 260 258 Gastrointestinal Disorders 84 (32) 93 (36) Diarrhea 27 (10) 29 (11) Nausea 20 (8) 23 (9) Vomiting 17 (7) 17 (7) General Disorders/Administration Site Conditions 52 (20) 45 (17) Pyrexia 34 (13) 21 (8) Nervous System Disorders 42 (16) 40 (16) Headache 22 (9) 20 (8) Vascular Disorders 54 (21) 21 (8) Phlebitis 49 (19) 13 (5) Skin and Subcutaneous Tissue Disorders 36 (14) 26 (10) Rash 14 (5) 6 (2) 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 MYCAMINE (382) or fluconazole (409) experienced at least one adverse reaction during the study. Treatment-emergent adverse reactions resulting in MYCAMINE discontinuation were reported in 15 (4%) adult patients; while those resulting in fluconazole discontinuation were reported in 32 (8%).

Drug interactions

Monitor for sirolimus, itraconazole or nifedipine toxicity, and dosage of sirolimus, itraconazole or nifedipine should be reduced, if necessary. ( 7 ) 7.1 Effect of Other Drugs on MYCAMINE CYP3A4, CYP2C9 and CYP2C19 Inhibitors Co-administration of MYCAMINE with cyclosporine, itraconazole, voriconazole and fluconazole did not alter the pharmacokinetics of MYCAMINE. CYP2C19 and CYP3A4 Inducer Co-administration of MYCAMINE with rifampin and ritonavir did not alter the pharmacokinetics of MYCAMINE. Co-administration of MYCAMINE with Other Drugs Co-administration of MYCAMINE with mycophenolate mofetil (MMF), amphotericin B, tacrolimus, prednisolone, sirolimus and nifedipine did not alter the pharmacokinetics of MYCAMINE. 7.2 Effect of MYCAMINE on Other Drugs CYP3A4 Substrates There was no effect of single or multiple doses of MYCAMINE on cyclosporine, tacrolimus, prednisolone, voriconazole and fluconazole pharmacokinetics. Sirolimus AUC was increased by 21% with no effect on C max in the presence of steady-state MYCAMINE compared with sirolimus alone. Nifedipine AUC and C max were increased by 18% and 42%, respectively, in the presence of steady-state MYCAMINE compared with nifedipine alone. Itraconazole AUC and C max were increased by 22% and 11%, respectively. Patients receiving sirolimus, nifedipine, and itraconazole in combination with MYCAMINE should be monitored for sirolimus, nifedipine, and itraconazole toxicity and the sirolimus, nifedipine, and itraconazole dosage should be reduced if necessary. UDP-Glycosyltransferase Substrate Co-administration of mycophenolate mofetil (MMF) with MYCAMINE did not alter the pharmacokinetics of MMF.

Use in specific populations

Pregnancy – Based on animal data, MYCAMINE may cause fetal harm. Advise pregnant women of the risk to the fetus. ( 8.1 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies, MYCAMINE may cause fetal harm when administered to a pregnant woman (see Data ) . There is insufficient human data on the use of MYCAMINE 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 (see Data ) . 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. 8.2 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 MYCAMINE, and any potential adverse effects on the breast-fed child from MYCAMINE, or from the underlying maternal condition. 8.4 Pediatric Use Pediatric Patients 4 Months of Age and Older The safety and effectiveness of MYCAMINE 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 MYCAMINE 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 [see Indications and Usage ( 1 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14 )]. 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 MYCAMINE 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 MYCAMINE 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 [see Adverse Reactions ( 6.1 ) and Clinical Pharmacology ( 12.3 )] . 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 MYCAMINE 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 [see Microbiology ( 12.4 )] . 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 MYCAMINE 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 MYCAMINE-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 MYCAMINE and 10 treated with amphotericin B) which was 13% of the planned enrollment for the study, no conclusions can be drawn regarding efficacy of MYCAMINE at this dose regimen.

Pregnancy

8.1 Pregnancy Risk Summary Based on findings from animal studies, MYCAMINE may cause fetal harm when administered to a pregnant woman (see Data ) . There is insufficient human data on the use of MYCAMINE 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 (see Data ) . 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.

Pediatric use

8.4 Pediatric Use Pediatric Patients 4 Months of Age and Older The safety and effectiveness of MYCAMINE 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 MYCAMINE 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 [see Indications and Usage ( 1 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14 )]. 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 MYCAMINE 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 MYCAMINE 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 [see Adverse Reactions ( 6.1 ) and Clinical Pharmacology ( 12.3 )] . 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 MYCAMINE 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 [see Microbiology ( 12.4 )] . 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 MYCAMINE 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 MYCAMINE-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 MYCAMINE and 10 treated with amphotericin B) which was 13% of the planned enrollment for the study, no conclusions can be drawn regarding efficacy of MYCAMINE 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 MYCAMINE at dose regimens ranging from 5 to 15 mg/kg once daily. Across the entire MYCAMINE 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 MYCAMINE 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 MYCAMINE 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 MYCAMINE 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 MYCAMINE 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

8.5 Geriatric Use A total of 418 subjects in clinical studies of MYCAMINE 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 MYCAMINE 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.

Overdosage

10 OVERDOSAGE MYCAMINE is highly protein bound and, therefore, is not dialyzable. No cases of MYCAMINE overdosage have been reported. Repeated daily doses up to 8 mg/kg (maximum total dose of 896 mg) in adult patients, up to 6 mg/kg in pediatric patients 4 months of age and older, and up to 15 mg/kg in pediatric patients younger than 4 months of age have been administered in clinical trials with no reported dose-limiting toxicity [see Adverse Reactions ( 6.1 ) and Use in Specific Populations ( 8.4 )].

Description

11 DESCRIPTION MYCAMINE is a sterile, lyophilized product for intravenous (IV) infusion that contains micafungin sodium. Micafungin sodium is a semisynthetic lipopeptide (echinocandin) synthesized by a chemical modification of a fermentation product of Coleophoma empetri F-11899. Micafungin inhibits the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall. Each single-dose vial contains 50 mg micafungin (equivalent to 50.86 mg micafungin sodium) or 100 mg micafungin (equivalent to 101.73 mg micafungin sodium), 200 mg lactose monohydrate, with citric acid and/or sodium hydroxide (used for pH adjustment). MYCAMINE must be diluted with 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP [see Dosage and Administration ( 2 )] . Following reconstitution with 0.9% Sodium Chloride Injection, USP, the resulting pH of the solution is between 5-7. Micafungin sodium is chemically designated as: Pneumocandin A0,1-[(4 R ,5 R )-4,5-dihydroxy- N 2 -[4-[5-[4-(pentyloxy) phenyl]-3-isoxazolyl]benzoyl]-L-ornithine]-4-[(4 S )-4-hydroxy-4-[4-hydroxy-3-(sulfooxy)phenyl]-L-threonine]-, monosodium salt. The chemical structure of micafungin sodium is: The empirical/molecular formula is C 56 H 70 N 9 NaO 23 S and the formula weight is 1292.26. Micafungin sodium is a light-sensitive, hygroscopic white powder that is freely soluble in water, isotonic sodium chloride solution, N,N-dimethylformamide and dimethylsulfoxide, slightly soluble in methyl alcohol, and practically insoluble in acetonitrile, ethyl alcohol (95%), acetone, diethyl ether and n-hexane. Micafungin sodium structural formula

Mechanism of action

12.1 Mechanism of Action Micafungin is a member of the echinocandin class of antifungal agents [see Microbiology ( 12.4 )] .

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING MYCAMINE is supplied as a sterile, white lyophilized powder for reconstitution for intravenous infusion, and is available in the following packaging configurations:
• cartons of 10 individually packaged 50 mg single-dose vials, coated with a light protective film and sealed with a blue flip-off cap. (NDC 0469-3250-10)
• cartons of 10 individually packaged 100 mg single-dose vials, coated with a light protective film and sealed with a red flip-off cap. (NDC 0469-3211-10) Storage Unopened vials of lyophilized material must be stored at room temperature, 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Store the reconstituted product at 25°C (77°F) [ see Dosage and Administration ( 2.4 )] Store the diluted solution at 25°C (77°F) [ see Dosage and Administration ( 2.4 )] Protect from light.

Patient information

Hypersensitivity Inform patients about the serious adverse effects of MYCAMINE including hypersensitivity reactions e.g., anaphylaxis and anaphylactoid reactions including shock. Hepatic Inform patients about the serious adverse effects of MYCAMINE including hepatic effects e.g., abnormal liver tests, hepatic impairment, hepatitis or worsening hepatic failure. Hematologic Inform patients about the serious adverse effects of MYCAMINE including hematological effects e.g., acute intravascular hemolysis, hemolytic anemia and hemoglobinuria. Renal Inform patients about the serious adverse effects of MYCAMINE including renal effects e.g., elevations in BUN and creatinine, renal impairment or acute renal failure. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk of MYCAMINE to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy. Concomitant Medications Instruct patients to inform their healthcare provider of any other medications they are currently taking with MYCAMINE, including over-the-counter medications. Manufactured by: Astellas Pharma Tech Co., Ltd. Takaoka Plant 30 Toidesakae-machi, Takaoka city, Toyama 939-1118, Japan Marketed by: Astellas Pharma US, Inc. Northbrook, IL 60062 USA MYCAMINE ® is a registered trademark of Astellas Pharma Inc. 286316-MYC

Label text from the FDA structured product label by Astellas Pharma US, Inc. (revised Jul 23, 2020). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Micafungin Sodium in 1 product

Mycamine NDC products (1)

NDC	Strength & form	Labeler	Type
0469-3250	Micafungin Sodium 10 mg/mL Injection, Powder, Lyophilized, For Solution	Astellas Pharma US, Inc.	NDA

Mycamine recalls

D-0548-2018 Feb 14, 2018 · Class II · Terminated
Labeling: Label Error on Declared Strength

Frequently asked questions

What is Mycamine used for?

What are the side effects of Mycamine?

Who makes Mycamine?

Mycamine is listed by 1 labeler in the FDA NDC directory, including Astellas Pharma US, Inc..

Has Mycamine been recalled?

The FDA enforcement database lists 1 recall for Mycamine, most recently D-0548-2018 (class ii): Labeling: Label Error on Declared Strength