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 )
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 )
5.1Hypersensitivity 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.
5.2Hematological 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.
5.3Hepatic 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.
5.4Renal 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.
5.5Infusion 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 )] .
Interactions
Monitor for sirolimus, itraconazole or nifedipine toxicity, and dosage of sirolimus, itraconazole or nifedipine should be reduced, if necessary. ( 7 )
7.1Effect 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.
7.2Effect 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.
Pregnancy and breastfeeding
8.1Pregnancy 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.
Adverse reactions
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 .
6.1Clinical 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%). Selected adverse reactions reported in 15% or more of adult patients and more frequently in the MYCAMINE 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 Patient base: all randomized adult patients who received at least 1 dose of trial drug. System Organ Class MYCAMINE 50 mg/day n (%) Fluconazole 400 mg/day n (%) Number of Patients 382 409 Gastrointestinal Disorders 377 (99) 404 (99) Diarrhea 294 (77) 327 (80) Nausea 270 (71) 290 (71) Vomiting 252 (66) 274 (67) Abdominal Pain 100 (26) 93 (23) Blood and Lymphatic System Disorders 368 (96) 385 (94) Neutropenia 288 (75) 297 (73) Thrombocytopenia 286 (75) 280 (69) Skin and Subcutaneous Tissue Disorders 257 (67) 275 (67) Rash 95 (25) 91 (22) Nervous System Disorders 250 (65) 254 (62) Headache 169 (44) 154 (38) Psychiatric Disorders 233 (61) 235 (58) Insomnia 142 (37) 140 (34) Anxiety 84 (22) 87 (21) Cardiac Disorders 133 (35) 138 (34) Tachycardia 99 (26) 91 (22) 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
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 MYCAMINE was assessed in 593 pediatric patients, 425 of whom were 4 months through 16 years of age and 1
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Composition
Active ingredients
MICAFUNGIN SODIUM EQ 100MG BASE/VIAL
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
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