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Micafungin Sodium

FDA Drug Information • Also known as: Micafungin, Mycamine

Brand Names
Micafungin, Mycamine
Route
INTRAVENOUS
Dosage Form
INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Micafungin for Injection 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, with citric acid and/or sodium hydroxide (used for pH adjustment). Micafungin for Injection 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: C 56 H 70 N 9 NaO 23 S M.W. 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. micaf-struc-01.jpg

What Is Micafungin Sodium Used For?

1 INDICATIONS AND USAGE 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 [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 )] . Micafungin for Injection 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 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 . ( 1 )
  • The efficacy of Micafungin for Injection against infections caused by fungi other than Candida has not been established. ( 1 ) 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 [see Use in Specific Populations ( 8.4 )] .
  • 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.

    • Dosage and Administration

    2 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. Micafungin for Injection Dosage in Adult Patients * 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). 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 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. 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) 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 Micafungin for Injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients...

    • Side Effects (Adverse Reactions)

    6 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 Fresenius Kabi USA, LLC at 1-800-551-7176 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 micafungin 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 was assessed in 520 healthy volunteers and 3417 adult and pediatric patients who received single or multiple doses of micafungin across 50 clinical trials, including the invasive candidiasis, esophageal candidiasis and prophylaxis trials. The doses of micafungin 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 micafungin, 2,497/2,748 (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 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 treatment group, are shown in Table 3 . Table 3. Selected * 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. * 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). Adverse Reaction by System Organ Class † Micafungin 100 mg n (%) 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 micafungin (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 and amphotericin B liposome treatment groups, respectively: nausea (10% vs. 8%), diarrhea (11% vs. 11%), vomiting (13% vs. 9%), abnormal liver function tests (4% vs. 3%), increased aspartate aminotransferase (3% vs. 2%), and...

    • Drug Interactions

    7 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 Micafungin CYP3A4, CYP2C9 and CYP2C19 Inhibitors Co-administration of micafungin with cyclosporine, itraconazole, voriconazole and fluconazole did not alter the pharmacokinetics of micafungin. CYP2C19 and CYP3A4 Inducer Co-administration of micafungin with rifampin and ritonavir did not alter the pharmacokinetics of micafungin Co-administration of Micafungin with Other Drugs Co-administration of micafungin with mycophenolate mofetil (MMF), amphotericin B, tacrolimus, prednisolone, sirolimus and nifedipine did not alter the pharmacokinetics of micafungin. 7.2 Effect of Micafungin on Other Drugs CYP3A4 Substrates There was no effect of single or multiple doses of micafungin 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 micafungin compared with sirolimus alone. Nifedipine AUC and C max were increased by 18% and 42%, respectively, in the presence of steady-state micafungin 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 micafungin 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 micafungin did not alter the pharmacokinetics of MMF.

    Contraindications

    4 CONTRAINDICATIONS 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. ( 4 )

    Pregnancy and Breastfeeding

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

    Overdosage

    10 OVERDOSAGE Micafungin is highly protein bound and, therefore, is not dialyzable. No cases of micafungin 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 )] .

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Micafungin for Injection is supplied as a sterile, white lyophilized powder for reconstitution for intravenous infusion, and is available in the following packaging configurations: Product Code Unit of Sale Strength Each 728110 NDC 63323-728-10 Unit of 10 packaged in individual cartons. 50 mg per vial NDC 63323-728-01 10 mL single dose vial coated with a light protective flap and sealed with a blue flip off cap. 729110 NDC 63323-729-10 Unit of 10 packaged in individual cartons. 100 mg per vial NDC 63323-729-01 10 mL single dose vial coated with a light protective flap and sealed with a red flip off cap. 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.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.