Micafungin Sodium (Mycamine ®)
Drug UPDATES: [Drug information (pdf)]
PACKAGE INSERT -Dosing: Click (+) next to Dosage and Administration section (drug info link)
[ 150 mg ] [100 ml] [1 hour]
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
Stability*: 24 hours room temperature.
*Translation: the manufacturer is likely moving to a shorter stability time (12 hours) which is reflected in the most recently revised monograph from Par Pharmaceuticals.
Label: Protect from light.
Micafungin for injection is a sterile, white 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 anhydrous 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 to 7.
Micafungin is a member of the echinocandin class of antifungal agents
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 has 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 contraindicated in persons with known hypersensitivity to micafungin, any component of micafungin for injection, or other echinocandins.
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.
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.
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.
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.
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 [see Dosage and Administration (2.3)].
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 [see Dosage and Administration (2.3) and Adverse Reactions (6.1)].
- 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: Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. Drug information
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).
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) | |
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 has 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)].
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:
1. 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.
2. Appropriately label the bag.
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1. Calculate the total micafungin for injection 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 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).
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. 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 [see Warnings and Precautions (5.5)].
5. 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.
Administer micafungin for injection by intravenous infusion only. Infuse over one hour. More rapid infusions may result in more frequent histamine-mediated reactions [see Warnings and Precautions (5.5)].
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 [see Warnings and Precautions (5.5)].
Micafungin for injection is a sterile, white lyophilized powder for reconstitution for intravenous infusion available as:
- 50 mg single-dose vial
- 100 mg single-dose vial
Micafungin for injection 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 royal blue flip-off button. (NDC 60505-6119-5).
- •cartons of 10 individually packaged 100 mg single-dose vials, coated with a light protective film and sealed with a red flip-off button. (NDC 60505-6120-6).
Storage
Unopened vials of lyophilized material must be stored at room temperature, Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 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
