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MYCAMINE (micafungin sodium) For Injection; IV Infusion
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use MYCAMINE ® safely and effectively. See Full Prescribing Information for MYCAMINE.
MYCAMINE (micafungin sodium) For Injection; IV Infusion Only
Initial U.S. Approval: 2005
RECENT MAJOR CHANGES
Indications and Usage (1) 06/2013
Dosage and Administration (2) 06/2013
INDICATIONS AND USAGE
Mycamine is an echinocandin indicated in adult and pediatric patients 4 months and older for:
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Treatment of Patients with Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses ( 1.1)
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Treatment of Patients with Esophageal Candidiasis ( 1.2)
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Prophylaxis of Candida Infections in Patients Undergoing Hematopoietic Stem Cell Transplantation ( 1.3)
DOSAGE AND ADMINISTRATION
Recommended Reconstituted Dose Once Daily By Indication
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Indication
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Dose
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Adult
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Pediatric 30 kg or less
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Pediatric greater than
30 kg
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Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses (1.1)
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100 mg daily
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2 mg/kg/day
(maximum 100 mg daily)
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Treatment of Esophageal Candidiasis (1.2)
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150 mg daily
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3 mg/kg/day
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2.5 mg/kg/day
(maximum150 mg daily)
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Prophylaxis of Candida Infections in HSCT Recipients (1.3)
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50 mg daily
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1 mg/kg/day
(maximum 50 mg daily)
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A loading dose is not required. Infuse over 1 hour. ( 2.1, 2.4)
See Full Prescribing Information for IV administration instructions (2)
DOSAGE FORMS AND STRENGTHS
50 mg and 100 mg single-use vials (3)
CONTRAINDICATIONS
Mycamine is contraindicated in persons with known hypersensitivity to micafungin sodium, any component of Mycamine, or other echinocandins. (4)
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
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Anaphylaxis and anaphylactoid reactions (including shock) have been observed. Discontinue Mycamine and administer appropriate treatment ( 5.1)
Hematological Effects
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Isolated cases of acute intravascular hemolysis, hemolytic anemia and hemoglobinuria have been reported ( 5.2)
Hepatic Effects
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Abnormalities in liver function tests; isolated cases of hepatic impairment, hepatitis, and hepatic failure have been observed ( 5.3)
Renal Effects
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Elevations in BUN and creatinine; isolated cases of renal impairment or acute renal failure have been reported ( 5.4)
Monitor closely patients who develop clinical or laboratory evidence of the above reactions and eva luate risk/benefit of continuing Mycamine therapy. (5)
ADVERSE REACTIONS
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Most common adverse reactions include diarrhea, nausea, vomiting, pyrexia, thrombocytopenia, and headache ( 6)
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Histamine-mediated symptoms including rash, pruritus, facial swelling, and vasodilatation ( 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.
DRUG INTERACTIONS
Monitor for sirolimus, itraconazole or nifedipine toxicity, and dosage of sirolimus, itraconazole or nifedipine should be reduced, if necessary (7)
USE IN SPECIFIC POPULATIONS
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Pregnancy - No human data. Adverse effects in animals. Use if potential benefits of treatment outweigh potential fetal risk ( 8.1)
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Nursing Mothers - Caution should be exercised if administered to a nursing woman ( 8.3)
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Safety and effectiveness in pediatric patients less than 4 months of age have not been established ( 8.4)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 6/2013
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
Mycamine® is indicated in adult and pediatric patients 4 months and older for:
1.1 Treatment of Patients with Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses
[see Clinical Studies (14.1)]
Mycamine has not been adequately studied in patients with endocarditis, osteomyelitis and meningitis due to Candida infections.
1.3 Prophylaxis of Candida Infections in Patients Undergoing Hematopoietic Stem Cell Transplantation
[see Clinical Studies (14.3)]
NOTE: The efficacy of Mycamine against infections caused by fungi other than Candida has not been established.
2 DOSAGE AND ADMINISTRATION
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.
The recommended doses for adult patients based on indications are shown in Table 1.
2.1 Dose and Schedule for Adults
A loading dose is not required. Typically, 85% of the steady-state concentration is achieved after three daily Mycamine doses.
No dosing adjustments are required based on race, gender, or in patients with severe renal impairment or in patients with mild, moderate, or severe hepatic impairment [see Use in Specific Populations (8)].
No dose adjustment for Mycamine is required with concomitant use of mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, sirolimus, nifedipine, fluconazole, voriconazole, itraconazole, amphotericin B, ritonavir, or rifampin [see Drug Interactions (7)].
2.2 Dose and Schedule for Pediatric Patients
The recommended doses for pediatric patients based on indication and weight are shown in Table 2.
2.3 Directions for Reconstitution, Dilution, and Preparation
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:
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0.9% Sodium Chloride Injection, USP (without a bacteriostatic agent).
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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 sodium.
Mycamine 100 mg vial: after reconstitution each mL contains 20 mg of micafungin sodium.
As with all parenteral drug products, reconstituted Mycamine should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use material 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.
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:
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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.
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Appropriately label the bag.
Pediatric Patients:
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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).
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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.
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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).
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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.
Note: To minimize the risk of infusion reactions, concentrations of greater than 1.5 mg/mL should be administered via central catheter [see Adverse Reactions (6.1)].
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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.
Mycamine is preservative-free. Discard partially used vials.
2.4 Infusion Volume and Duration
Mycamine should be administered by intravenous infusion only. Infuse over one hour. More rapid infusions may result in more frequent histamine mediated reactions.
An existing intravenous line should be flushed with 0.9% Sodium Chloride Injection, USP, prior to infusion of Mycamine.
Pediatric Patients
Mycamine should be infused over one hour. To minimize the risk of infusion reactions, concentrations of greater than 1.5 mg/mL should be administered via central catheter [see Adverse Reactions (6.1)].
3 DOSAGE FORMS AND STRENGTHS
50 mg and 100 mg single-use vials
4 CONTRAINDICATIONS
Mycamine is contraindicated in persons with known hypersensitivity to micafungin, any component of Mycamine, or other echinocandins.
5 WARNINGS AND PRECAUTIONS
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). This reaction was transient, and the subject did not develop significant anemia. Isolated 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 eva luated 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 eva luated 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.
6 ADVERSE REACTIONS
The overall safety of Mycamine was assessed in 3227 adult and pediatric patients and 520 volunteers in 46 clinical trials, including the invasive candidiasis, esophageal candidiasis and prophylaxis trials, who received single or multiple doses of Mycamine, ranging from 0.75 mg/kg to 10 mg/kg in pediatric patients and 12.5 mg to 150 mg/day or greater in adult patients.
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 adverse reaction information from clinical trials does provide a basis for identifying adverse events that appear to be related to drug use and for approximating rates.
6.1 Infusion Reactions
Possible histamine-mediated symptoms have been reported with Mycamine, including rash, pruritus, facial swelling, and vasodilatation.
Injection site reactions, including phlebitis and thrombophlebitis have been reported, at Mycamine doses of 50-150 mg/day. These reactions tended to occur more often in patients receiving Mycamine via peripheral intravenous administration.
6.2 Clinical Trials Experience in Adults
In all clinical trials with Mycamine, 2497/2748 (91%) adult patients experienced at least one treatment-emergent adverse reaction.
Candidemia and Other Candida Infections
In a randomized, double-blind study for treatment of candidemia and other Candida infections, treatment-emergent adverse reactions occurred in 183/200 (92%), 187/202 (93%) and 171/193 (89%) patients in the Mycamine 100 mg/day, Mycamine 150 mg/day, and caspofungin (a 70 mg loading dose followed by a 50 mg/day dose) treatment groups, respectively. Selected treatment-emergent adverse reactions, those occurring in 5% or more of the patients and more frequently in a Mycamine treatment group, are shown in Table 3.
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