MYCAMINE (Brand for MICAFUNGIN)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Discard solution if evidence of precipitation or foreign matter is observed. Micafungin is a clear and colorless solution.
Intravenous Administration
Single-dose vials
Reconstitution
-Reconstitute each 50 or 100 mg vial with 5 mL of 0.9% Sodium Chloride Injection (without bacteriostatic agent) or 5% Dextrose Injection to yield 10 or 20 mg/mL, respectively.
-Gently dissolve the powder by swirling the vial. In order to minimize excessive foaming, do not vigorously shake the vial.
-Storage: Reconstituted micafungin may be stored in the original vial protected from light for up to 24 hours at room temperature (25 degrees C or 77 degrees F).

Dilution
-Withdraw the calculated volume of reconstituted micafungin and add to an IV bag or syringe containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection. Ensure the final concentration of the diluted solution is between 0.5 to 4 mg/mL. Label infusion bags or syringes containing micafungin concentrations more than 1.5 mg/mL for administration through a central catheter only.
-Storage: The final diluted solution may be stored protected from light for up to 24 hours at room temperature (25 degrees C or 77 degrees F). Discard partially used vials; the single-dose vial of micafungin is preservative-free.

Galaxy containers
-No further dilution is necessary.
-Suspend the container from support.
-Remove the protector from the outlet port at bottom of container.
-Attach an IV administration set to the outlet port. Refer to the manufacturer's instructions accompanying the administration set for complete directions.
-Check for minute leaks by squeezing the container firmly. If leaks are detected, discard the solution as sterility may be impaired.
-Storage: The Galaxy container of micafungin may be stored for up to 30 days at room temperature up to 25 degrees C (77 degrees F). If stored at room temperature, discard the Galaxy container of micafungin after 30 days. Once stored at room temperature, do not place the Galaxy container of micafungin back into the refrigerator. Do not freeze. Discard partially used bags; the Galaxy container of micafungin is preservative-free.

Intermittent IV Infusion
-To minimize the risk of infusion-related reactions, infuse solutions with concentrations more than 1.5 mg/mL via a central catheter.
-If an existing IV line will be used, flush the line with 0.9% Sodium Chloride Injection before infusing micafungin.
-Administer as a slow IV infusion over 1 hour. If administered more rapidly, more frequent histamine-mediated reactions may occur. Do not administer as an IV bolus injection.
-Do not mix or co-infuse micafungin with other medications. Micafungin has been shown to precipitate when mixed directly with several commonly used medications.
-Protect diluted micafungin from light; however, it is not necessary to cover the infusion drip chamber or the tubing during administration.

The safety of micafungin was assessed in 15 pediatric trials, which included 425 pediatric patients who were 4 months through 16 years of age and 168 pediatric patients who were 3 days to less than 4 months of age. The adverse reaction profile of micafungin in pediatric patients younger than 4 months of age was generally comparable to that of pediatric patients 4 months of age and older and adults. No new safety concerns were observed with micafungin 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 reactions.

Hematologic adverse events, including thrombocytopenia (9% to 72%), neutropenia (5% to 77%), febrile neutropenia (16%), anemia (15% to 51%), leukocytosis (less than 15%), thrombocytosis (less than 15%), neonatal coagulation disorder (less than 15%), and epistaxis (9%) have been reported in pediatric patients receiving micafungin in clinical trials. Other hematologic and lymphatic adverse events observed during adult trials, and potentially associated with micafungin, include coagulopathy, intracranial bleeding, hemolysis, hemolytic anemia, pancytopenia, and thrombotic thrombocytopenic purpura (TTP). Cases of disseminated intravascular coagulation (DIC) have been reported during postmarketing use. Patients should be monitored carefully for clinical or laboratory evidence of hemolysis or reductions in blood counts. If clinical or laboratory evidence of hemolysis or hemolytic anemia occurs, closely monitor the patient for evidence of worsening of these conditions and evaluate the risk/benefit of continued therapy.

Rash (2% to 30%), pruritus (33%), and urticaria (19%) have been reported in pediatric patients treated with micafungin in clinical trials. Facial swelling and peripheral vasodilation have been reported in adult patients and are thought to be histamine-mediated infusion reactions. Cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported during postmarketing use of micafungin. Serious hypersensitivity reactions such as anaphylactic shock and anaphylactoid reactions have also occurred. If a serious hypersensitivity reaction occurs, discontinue micafungin and administer appropriate treatment.

Elevated hepatic enzymes have been reported in pediatric patients receiving micafungin in clinical trials. Specifically, elevated alanine aminotransferase (ALT) was reported in 16% of patients. Higher doses of micafungin (more than 4 mg/kg) have been associated with an increased frequency of elevated liver enzymes (approximately 14%) compared with doses less than 4 mg/kg (0% to 3%). Hyperbilirubinemia (less than 15%), abnormal liver function tests (less than 15%), and hepatomegaly (1.4%) have also been reported. Isolated cases of significant hepatic dysfunction, hepatitis, hepatic failure, hepatocellular damage, and jaundice have also been associated with micafungin. A case of micafungin-associated hepatitis was reported in a premature infant who received micafungin 8 mg/kg/day. Liver function gradually improved after micafungin discontinuation. Monitor patients who develop abnormal liver function tests during treatment with micafungin for evidence of worsening hepatic function. The risks and benefits of continued micafungin receipt need to be considered.

Metabolic disturbances, including hypokalemia (22% to 25%), acidosis (20%), sepsis (20%), dehydration (less than 15%), hyperglycemia (less than 15%), hypocalcemia (less than 15%), hypermagnesemia (less than 15%), increased lactate dehydrogenase (LDH; less than 15%), and elevated alkaline phosphatase (2%) have been reported in pediatric patients receiving micafungin in clinical trials. Other metabolic disturbances, such as hyperkalemia, hypernatremia, and hypoglycemia, were reported in adult patients receiving micafungin in clinical trials.

Neurological adverse reactions, including headache (15%) and anxiety (23%), have been reported in pediatric patients treated with micafungin in clinical trials. Although not specifically reported in pediatric trials, insomnia occurred in a large proportion (37%) of adult hematopoietic stem cell transplant recipients who received micafungin for Candida infection prophylaxis in 1 clinical trial; a similar percentage (34%) of patients who received fluconazole in the same trial also experienced insomnia. Other neurological adverse reactions reported in adult patients in clinical trials included delirium, convulsions or seizures, and encephalopathy.

Gastrointestinal adverse reactions, including vomiting (15% to 65%), diarrhea (7% to 51%), nausea (7% to 70%), mucosal inflammation (19%), abdominal pain (4% to 35%), and abdominal distention (2% to 19%), were commonly reported in pediatric patients treated with micafungin in clinical trials. Hematochezia, GI perforation, ascites, ileus, diarrhea, abdominal distension, and intestinal infarction were reported in less than 15% of pediatric patients younger than 4 months receiving micafungin in clinical trials.

Infusion-related reactions (16%) were reported in pediatric patients receiving micafungin in clinical trials. Fever (9% to 61%), hypotension (1.4%), and rigors (1%) have been reported. Infusion site extravasation, neonatal hypotension, generalized edema, fever, thrombophlebitis, and peripheral edema were also reported in less than 15% of pediatric patients younger than 4 months receiving micafungin in clinical trials. An injection site reaction, consisting of phlebitis, thrombophlebitis, and injection site thrombosis, has also been associated with the use of micafungin. Injection site reactions are more frequent in patients receiving micafungin via peripheral intravenous administration. To minimize the risk of infusion reactions, infuse solutions with concentrations more than 1.5 mg/mL via a central catheter.

Acute renal failure (unspecified; less than 15%), hematuria (23%), and oliguria (23%) have been reported in pediatric patients treated with micafungin in clinical trials. Azotemia (i.e., elevated BUN) has also been reported in pediatric patients. Renal effects, such as renal impairment, elevations in BUN and serum creatinine, and hemoglobinuria, have also occurred in adult patients receiving micafungin during clinical trials. Monitor patients who develop abnormal renal function tests during treatment with micafungin for possible worsening renal function.

Cardiovascular adverse reactions, including hypertension (15%) and sinus tachycardia (4% to 16%), have been reported in pediatric patients treated with micafungin in clinical trials. Prolonged QRS complex was reported in less than 15% of pediatric patients younger than 4 months receiving micafungin in clinical trials. Additional cardiovascular adverse reactions reported in adult patients receiving micafungin in clinical trials included atrial fibrillation, pericardial effusion, myocardial infarction, and cardiac arrest. Cases of vascular shock have been reported during the postmarketing period.

Decreased oxygen saturation was reported in 15% of pediatric patients younger than 4 months receiving micafungin in clinical trials. Pleural effusion, respiratory failure, neonatal aspiration, and respiratory distress (dyspnea) were also reported in less than 15% of patients.

Neonatal hypertonia was reported in less than 15% of pediatric patients younger than 4 months receiving micafungin in clinical trials.

Micafungin is contraindicated in patients with a known hypersensitivity to the drug or to any ingredients in the formulation of the product.

Use caution in patients with hepatic disease (e.g., cholestasis, hepatitis, or jaundice). Elevations in liver function tests and isolated cases of clinically significant hepatic impairment, hepatitis, and hepatic failure have been reported during micafungin therapy.

Use caution in patients with renal disease or renal impairment. Elevations in serum creatinine and BUN and isolated cases of significant renal dysfunction and acute renal failure have been reported in association with micafungin.

Infusion-related reactions (i.e., rash, pruritus, facial swelling, and vasodilation) and injection site reactions (i.e., phlebitis and thrombophlebitis) have been reported with micafungin at doses of 50 to 150 mg/day. These reactions tended to occur more frequently in patients receiving micafungin via peripheral intravenous administration. Slow the infusion rate if infusion reactions occur. To minimize the risk of infusion reactions, infuse solutions with concentrations more than 1.5 mg/mL via a central catheter.

Avoid use of the Galaxy container formulations of micafungin in Sodium Chloride Injection in persons with heart failure and those requiring sodium restriction due to the Galaxy container formulations containing sodium and risk for a high sodium load. Persons with heart failure and other conditions requiring restricted sodium intake may respond with a blunted natriuresis to salt loading.

Description: Micafungin is an intravenous antifungal agent belonging to the echinocandin class. Micafungin has good activity against Candida and Aspergillus species, and is active against many Candida isolates that are resistant to other antifungal agents such as fluconazole and amphotericin B. It has very little or no activity for other fungal infections such as cryptococcosis, zygomycosis, and fusariosis. Micafungin is used for the treatment of candidemia and invasive candidiasis, for the treatment of invasive aspergillosis that is refractory to or intolerant of other therapies, and for the prophylaxis of invasive fungal infections in high-risk patients (i.e., HSCT recipients). Micafungin is considered the echinocandin of choice in the neonatal population. Pharmacokinetic data have shown that a higher weight-based dose is required in neonates due to a higher drug clearance. Micafungin is FDA-approved for use in pediatric patients as young as neonates.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Candida albicans, Candida glabrata, Candida guilliermondii, Candida krusei, Candida parapsilosis, Candida tropicalis
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of candidemia and invasive candidiasis, including chronic disseminated (hepatosplenic) candidiasis*:
-for the treatment of candidemia and invasive candidiasis:
Intravenous dosage:
Neonates: 4 mg/kg/dose IV once daily. Safety and efficacy have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months as a higher dose may be needed. Doses as high as 10 to 15 mg/kg/dose IV once daily have been used off-label for CNS infections and have been shown to be necessary in these settings. Pharmacokinetic data derived from the use of Monte Carlo simulations have suggested that an appropriate neonatal dose, particularly for neonates with CNS infections, is between 9 to 15 mg/kg. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent.
Infants 1 to 3 months: 4 mg/kg/dose IV once daily. Safety and efficacy have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months as a higher dose may be needed. Treatment success with micafungin has ranged from 73% to 83%, and efficacy has been comparable to liposomal amphotericin B. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Guidelines recommend an echinocandin as initial therapy in both neutropenic and nonneutropenic patients.
Infants, Children, and Adolescents 4 months to 17 years weighing 40 kg or less: 2 mg/kg/dose IV once daily. If there is an inadequate clinical response after 5 days, may increase the dose to 4 mg/kg/dose IV once daily. Treatment success with micafungin has ranged from 73% to 83%, and efficacy has been comparable to liposomal amphotericin B. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Guidelines recommend an echinocandin as initial therapy in both neutropenic and nonneutropenic patients.
Children and Adolescents weighing more than 40 kg: 2 mg/kg/dose (Max: 100 mg/dose) IV once daily. If there is an inadequate clinical response after 5 days, may increase the dose to 200 mg IV once daily. Treatment success with micafungin has ranged from 73% to 83%, and efficacy has been comparable to liposomal amphotericin B. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Guidelines recommend an echinocandin as initial therapy in both neutropenic and nonneutropenic patients.
-for the treatment of chronic disseminated (hepatosplenic) candidiasis*:
Intravenous dosage:
Neonates: 4 mg/kg/dose IV once daily for several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent.
Infants 1 to 3 months: 4 mg/kg/dose IV once daily for several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate. Treatment success with micafungin has ranged from 73% to 83%, and efficacy has been comparable to liposomal amphotericin B.
Infants, Children, and Adolescents 4 months to 17 years weighing 40 kg or less: 2 mg/kg/dose IV once daily for several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate. If there is an inadequate clinical response after 5 days, may increase the dose to 4 mg/kg/dose IV once daily. Treatment success with micafungin has ranged from 73% to 83%, and efficacy has been comparable to liposomal amphotericin B.
Children and Adolescents weighing more than 40 kg: 2 mg/kg/dose (Max: 100 mg/dose) IV once daily for several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate. If there is an inadequate clinical response after 5 days, may increase the dose to 200 mg IV once daily. Treatment success with micafungin has ranged from 73% to 83%, and efficacy has been comparable to liposomal amphotericin B.

For the treatment of invasive aspergillosis* in patients who are refractory to or intolerant of other antifungal therapies:
Intravenous dosage:
Premature and Term Neonates: Data on micafungin use for aspergillosis in neonates are lacking. A dose of 7 to 10 mg/kg/dose IV once daily is recommended for most infections based on studies of micafungin use for invasive candidiasis, with the highest dose recommended for premature, very-low-birth-weight neonates. Doses up to 15 mg/kg/day have been used in premature neonates, particularly for CNS infections. One case report describes the successful use of micafungin (8 mg/kg/day) in combination with voriconazole and liposomal amphotericin B in a premature neonate with cutaneous aspergillosis. Although specific neonatal recommendations are not available, guidelines recommend micafungin as salvage therapy or in settings in which azole and polyene antifungals are contraindicated. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Infants and Children: Limited data are available; the optimal dosage has not been clearly defined. A dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Guidelines recommend micafungin as salvage therapy or in settings in which azole and polyene antifungals are contraindicated. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.
Adolescents: Limited data are available; the optimal dosage has not been clearly defined. 100 to 150 mg IV once daily is recommended in HIV-infected patients. Alternately, a dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Guidelines recommend micafungin as salvage therapy or in settings in which azole and polyene antifungals are contraindicated. Treat for at least 6 to 12 weeks with duration dependent on extent and length of immunosuppression, infection site, and disease improvement.

For the treatment of esophageal candidiasis, including fluconazole-refractory disease:
Intravenous dosage:
Infants 1 to 3 months*: Optimal dosing is not well established. 5 to 7 mg/kg/dose IV once daily for 14 to 21 days as an alternative.
Infants and Children 4 months and older weighing 30 kg or less: 3 mg/kg/dose IV once daily for 14 to 21 days as an alternative.
Children and Adolescents weighing more than 30 kg: 2.5 mg/kg/dose (Max: 150 mg/dose) IV once daily for 14 to 21 days as an alternative.

For the treatment of fluconazole-refractory oropharyngeal candidiasis (thrush)*:
Intravenous dosage:
Infants 1 to 3 months: Optimal dosing is not well established. 5 to 7 mg/kg/dose IV once daily for up to 28 days as an alternative.
Infants and Children 4 months and older weighing 30 kg or less: 3 mg/kg/dose IV once daily for up to 28 days as an alternative.
Children and Adolescents weighing more than 30 kg: 2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for up to 28 days as an alternative.

For the treatment of cardiovascular system infections, including endocarditis*, suppurative thrombophlebitis*, and infected pacemaker*, implantable cardiac defibrillator (ICD)*, or ventricular assist devices (VAD)*:
-for the treatment of Candida cardiovascular system infections*:
Intravenous dosage:
Premature Neonates weighing less than 1000 g: Limited data are available. 10 mg/kg/dose IV once daily is a commonly reported dosage ; however, doses up to 15 mg/kg/dose IV once daily have been used successfully for other infections (i.e., CNS infections). Pharmacokinetic data derived from the use of Monte Carlo simulations have suggested that an appropriate neonatal dose is between 9 to 15 mg/kg. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Premature Neonates weighing 1000 g or more and Term Neonates: Limited data are available. 7 to 10 mg/kg/dose IV once daily. Doses of 10 to 15 mg/kg/dose IV once daily have been used successfully for other infections (i.e., CNS infections). Pharmacokinetic data derived from the use of Monte Carlo simulations have suggested that an appropriate neonatal dose is between 9 to 15 mg/kg. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
Infants, Children, and Adolescents: 2 mg/kg/dose (Max: 100 mg/dose) IV once daily is the FDA-approved dosage for candidemia or acute disseminated candidiasis. Although the FDA-approved maximum dosage is 100 mg/day for candidemia or acute disseminated candidiasis, clinical practice guidelines recommend 150 mg IV once daily for adults with cardiac infections. If there is an inadequate clinical response after 5 days, may increase dose to 4 mg/kg/day for patients weighing 40 kg or less and 200 mg/day for patients weighing more than 40 kg. Treatment success with micafungin has ranged from 73% to 83% in clinical trials, and efficacy has been comparable to liposomal amphotericin B. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.
-for the treatment of Aspergillus cardiovascular system infections*:
Intravenous dosage:
Premature and Term Neonates: Data on micafungin use for aspergillosis in neonates are lacking. A dose of 7 to 10 mg/kg/dose IV once daily is recommended for most infections based on studies of micafungin use for invasive candidiasis, with the highest dose recommended for premature, very-low-birth-weight neonates. Doses up to 15 mg/kg/day have been used in premature neonates, particularly for CNS infections. One case report describes the successful use of micafungin (8 mg/kg/day) in combination with voriconazole and liposomal amphotericin B in a premature neonate with cutaneous aspergillosis. Recommended as alternative option for salvage therapy. Surgical resection of the infected valve or lesion followed by a minimum of 6 weeks of antifungal therapy is recommended; antifungal therapy alone is rarely successful. Consider life-long treatment with oral therapy to prevent recurrent infections.
Infants and Children: Limited data are available; the optimal dosage has not been clearly defined. A dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Recommended as alternative option for salvage therapy. Surgical resection of the infected valve or lesion followed by a minimum of 6 weeks of antifungal therapy is recommended; antifungal therapy alone is rarely successful. Consider life-long treatment with oral therapy to prevent recurrent infections.
Adolescents: Limited data are available; the optimal dosage has not been clearly defined. 100 to 150 mg IV once daily. Alternately, a dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Recommended as alternative option for salvage therapy. Surgical resection of the infected valve or lesion followed by a minimum of 6 weeks of antifungal therapy is recommended; antifungal therapy alone is rarely successful. Consider life-long treatment with oral therapy to prevent recurrent infections.

For the treatment of respiratory infections* (i.e., pneumonia*):
-for the treatment of Candida pneumonia:
Intravenous dosage:
Premature Neonates weighing less than 1000 g*: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Restrict treatment to pneumonia associated with disseminated infection. Limited data are available. 10 mg/kg/dose IV once daily is a commonly reported dosage ; however, doses up to 15 mg/kg/dose IV once daily have been used successfully for other infections (i.e., CNS infections). Pharmacokinetic data derived from the use of Monte Carlo simulations have suggested that an appropriate neonatal dose is between 9 to 15 mg/kg. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent.
Premature Neonates weighing 1000 g or more* and Term Neonates*: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Restrict treatment to pneumonia associated with disseminated infection. Limited data are available. 7 to 10 mg/kg/dose IV once daily for most infections. Doses of 10 to 15 mg/kg/dose IV once daily have been used successfully for other infections (i.e., CNS infections). Pharmacokinetic data derived from the use of Monte Carlo simulations have suggested that an appropriate neonatal dose is between 9 to 15 mg/kg. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent.
Infants, Children, and Adolescents: Growth of Candida sp. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. In cases where pneumonia is associated with disseminated infection, 2 mg/kg/dose IV (Max: 100 mg/dose) once daily.
-for the treatment of Aspergillus pneumonia:
Intravenous dosage:
Premature and Term Neonates: Data on micafungin use for aspergillosis in neonates are lacking. A dose of 7 to 10 mg/kg/dose IV once daily is recommended for most infections based on studies of micafungin use for invasive candidiasis, with the highest dose recommended for premature, very-low-birth-weight neonates. Doses up to 15 mg/kg/day have been used in premature neonates, particularly for CNS infections. One case report describes the successful use of micafungin (8 mg/kg/day) in combination with voriconazole and liposomal amphotericin B in a premature neonate with cutaneous aspergillosis. Recommended as alternative option for salvage therapy. The minimum duration of therapy is 6 to 12 weeks; however, total treatment duration depends on site of infection and immune status of the patient. For immunocompromised patients, treat throughout the duration of immunosuppression and until lesions have resolved.
Infants and Children: Limited data are available; the optimal dosage has not been clearly defined. A dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Recommended as alternative option for salvage therapy. The minimum duration of therapy is 6 to 12 weeks; however, total treatment duration depends on site of infection and immune status of the patient. For immunocompromised patients, treat throughout the duration of immunosuppression and until lesions have resolved.
Adolescents: Limited data are available; the optimal dosage has not been clearly defined. 100 to 150 mg IV once daily. Alternately, a dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Recommended as alternate option for salvage therapy. The minimum duration of therapy is 6 to 12 weeks; however, total treatment duration depends on site of infection and immune status of the patient. For immunocompromised patients, treat throughout the duration of immunosuppression and until lesions have resolved.

For the treatment of intraabdominal infections (i.e., peritonitis, intraabdominal abscess) including intraabdominal candidiasis and peritoneal dialysis-related peritonitis*:
-for the treatment of intraabdominal candidiasis:
Intravenous dosage:
Neonates: 4 mg/kg/dose IV once daily.
Infants 1 to 3 months: 4 mg/kg/dose IV once daily.
Infants, Children, and Adolescents 4 months to 17 years weighing 40 kg or less: 2 mg/kg/dose IV once daily. If there is an inadequate clinical response after 5 days, may increase dose to 4 mg/kg/dose IV once daily.
Children and Adolescents weighing more than 40 kg: 2 mg/kg/dose (Max: 100 mg/dose) IV once daily. If there is an inadequate clinical response after 5 days, may increase the dose to 200 mg IV once daily.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intravenous dosage:
Infants, Children, and Adolescents weighing less than 40 kg: Limited data are available; the optimal dosage has not been clearly defined. A dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments up to a maximum of 4.5 mg/kg/day. Treat for at least 14 days after catheter removal for Candida and as salvage therapy for Aspergillus.
Children and Adolescents weighing 40 kg or more: Limited data are available; the optimal dosage has not been clearly defined. 100 to 150 mg IV once daily is the adult dose. Alternately, a dosage regimen used in several studies is an initial dose of 75 mg IV once daily. For inadequate clinical response after 5 to 7 days, the dosage was increased in 75 mg/day increments up to a maximum of 225 mg/day. Treat for at least 14 days after catheter removal for Candida and as salvage therapy for Aspergillus.

For the treatment of bone and joint infections*, including osteomyelitis* and infectious arthritis*:
-for the treatment of Candida osteomyelitis or infectious arthritis:
Intravenous dosage:
Premature Neonates weighing less than 1000 g: Limited data are available. 10 mg/kg/dose IV once daily is a commonly reported dosage ; however, doses up to 15 mg/kg/dose IV once daily have been used successfully for other infections (i.e., CNS infections). Pharmacokinetic data derived from the use of Monte Carlo simulations have suggested that an appropriate neonatal dose is between 9 to 15 mg/kg. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis.
Premature Neonates weighing 1000 g or more and Term Neonates: Limited data are available. 7 to 10 mg/kg/dose IV once daily for most infections. Doses of 10 to 15 mg/kg/dose IV once daily have been used successfully for other infections (i.e., CNS infections). Pharmacokinetic data derived from the use of Monte Carlo simulations have suggested that an appropriate neonatal dose is between 9 to 15 mg/kg. For neonatal candidiasis, amphotericin B or fluconazole is the preferred therapy. Some experts state that if an echinocandin is used in neonates, micafungin is the preferred agent. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis.
Infants, Children, and Adolescents: 2 mg/kg/dose IV (Max: 100 mg/dose) once daily. If there is an inadequate clinical response after 5 days, may increase dose to 4 mg/kg/day for patients weighing 40 kg or less and 200 mg/day for patients weighing more than 40 kg. Treatment success with micafungin has ranged from 73% to 83% in clinical trials, and efficacy has been comparable to liposomal amphotericin B. Treat for at least 2 weeks followed by fluconazole for 6 to 12 months for osteomyelitis or 4 weeks for infectious arthritis. Recommended as an alternative to fluconazole as initial therapy. Surgical debridement may be helpful in some cases of osteomyelitis and is recommended for all cases of septic arthritis. For infection involving a prosthetic device, device removal in addition to antifungal therapy is recommended.
-for the treatment of Aspergillus osteomyelitis or infectious arthritis:
Intravenous dosage:
Premature and Term Neonates: Data on micafungin use for aspergillosis in neonates are lacking. A dose of 7 to 10 mg/kg/dose IV once daily is recommended for most infections based on studies of micafungin use for invasive candidiasis, with the highest dose recommended for premature, very-low-birth-weight neonates. Doses up to 15 mg/kg/day have been used in premature neonates, particularly for CNS infections. One case report describes the successful use of micafungin (8 mg/kg/day) in combination with voriconazole and liposomal amphotericin B in a premature neonate with cutaneous aspergillosis. Recommended as alternative option for salvage therapy. The minimum duration of treatment is 6 to 12 weeks; however, total treatment duration depends on site of infection and immune status of the patient. For immunocompromised patients, treat throughout the duration of immunosuppression. Consider long-term suppressive therapy.
Infants and Children: Limited data are available; the optimal dosage has not been clearly defined. A dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Recommended as alternative option for salvage therapy. The minimum duration of treatment is 6 to 12 weeks; however, total treatment duration depends on site of infection and immune status of the patient. For immunocompromised patients, treat throughout the duration of immunosuppression. Consider long-term suppressive therapy.
Adolescents: Limited data are available; the optimal dosage has not been clearly defined. 100 to 150 mg IV once daily. Alternately, a dosage regimen used in several studies is an initial dose of 1.5 mg/kg/dose IV once daily for patients weighing 40 kg or less and 75 mg IV once daily for patients weighing more than 40 kg. For inadequate clinical response after 5 to 7 days, the dosage was increased in 1.5 mg/kg/day increments (75 mg/day increments for those more than 40 kg) up to a maximum of 4.5 mg/kg/day (Max: 225 mg/day for those more than 40 kg). The maximum FDA-approved adult dosage is 150 mg/day. Recommended as alternative option for salvage therapy. The minimum duration of treatment is 6 to 12 weeks; however, total treatment duration depends on site of infection and immune status of the patient. For immunocompromised patients, treat throughout the duration of immunosuppression. Consider long-term suppressive therapy.

For candidiasis prophylaxis in high-risk patients (e.g., hematopoietic stem cell transplant recipients):
Intravenous dosage:
Neonates* and Infants 1 to 3 months*: Limited data are available. 1 mg/kg/dose IV once daily for a maximum of 6 weeks was used in a pharmacokinetic study in very low birth weight neonates in Japan (n = 25; gestational age less than 34 weeks; birthweight less than 1500 g). 1 mg/kg/day IV is also recommended in the European prescribing information for the prophylaxis of Candida infections in all pediatric patients weighing less than 40 kg, including neonates and infants. Recommended in patients with substantial risk of invasive candidiasis, such as allogeneic hematopoietic stem cell transplant (HSCT) recipients or those undergoing intensive remission-induction or salvage-induction chemotherapy for acute leukemia, and in patients with previous invasive aspergillosis, anticipated prolonged neutropenic periods of at least 2 weeks, or a prolonged period of neutropenia immediately prior to HSCT.
Infants 4 months and older, Children, and Adolescents: 1 mg/kg/dose IV (Max: 50 mg/dose) once daily. Higher doses (3 mg/kg/day) have also been reported in pediatric neutropenic patients receiving chemotherapy or hematopoietic stem cell transplant (HSCT). In 2 clinical studies in pediatric patients (n = 79 micafungin recipients), treatment success rates (defined as absence of proven, probable, or suspected invasive fungal infection) ranged from 69% to 80% for HSCT recipients and 94% for patients receiving chemotherapy. Treatment continued until ANC was 500 cells/mm3 or more or a maximum duration of 42 days after transplantation. Recommended in patients with substantial risk of invasive candidiasis, such as allogeneic hematopoietic stem cell transplant (HSCT) recipients or those undergoing intensive remission-induction or salvage-induction chemotherapy for acute leukemia, and in patients with previous invasive aspergillosis, anticipated prolonged neutropenic periods of at least 2 weeks, or a prolonged period of neutropenia immediately prior to HSCT.

For aspergillosis prophylaxis* in high-risk patients:
Intravenous dosage:
Infants, Children, and Adolescents: 1 mg/kg/dose IV once daily (Max: 50 mg/dose). Higher doses (3 mg/kg/day) have also been reported in pediatric neutropenic patients receiving chemotherapy or hematopoietic stem cell transplant (HSCT). In 2 clinical studies in pediatric patients (n = 79 micafungin recipients), treatment success rates (defined as absence of proven, probable, or suspected invasive fungal infection) ranged from 69% to 80% for HSCT recipients and 94% for patients receiving chemotherapy. Treatment continued until ANC was at least 500 cells/mm3 or until a maximum duration of 42 days after transplantation. Guidelines recommend micafungin prophylaxis as an alternative to posaconazole for high-risk patients, including allogeneic HSCT recipients with graft-versus-host disease (GVHD) and neutropenic patients with acute myelogenous leukemia or myelodysplastic disease.

For the treatment of asymptomatic candiduria in neutropenic persons:
Intravenous dosage:
Infants 1 to 3 months: 4 mg/kg/dose IV once daily for 14 days. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic persons; therefore, candiduria should be treated as disseminated candidiasis in these persons.
Infants, Children, and Adolescents 4 months to 17 years weighing 40 kg or less: 2 mg/kg/dose IV once daily for 14 days. May increase the dose to 4 mg/kg/dose IV once daily if there is an inadequate clinical response after 5 days. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic persons; therefore, candiduria should be treated as disseminated candidiasis in these persons.
Children and Adolescents weighing more than 40 kg: 2 mg/kg/dose (Max: 100 mg/dose) IV once daily for 14 days. May increase the dose to 200 mg IV once daily if there is an inadequate clinical response after 5 days. Candiduria may be the only microbiological documentation of disseminated candidiasis in neutropenic persons; therefore, candiduria should be treated as disseminated candidiasis in these persons.

Maximum Dosage Limits:
-Neonates
4 mg/kg/day IV is the FDA-approved maximum dosage; however, doses up to 15 mg/kg/day IV have been used off-label for CNS infections.
-Infants
1 to 3 months: 4 mg/kg/day IV is the FDA-approved maximum dosage; however, doses up to 4.5 mg/kg/day IV have been used off-label.
4 to 11 months: 3 mg/kg/day IV is the FDA-approved maximum dosage; however, doses up to 4.5 mg/kg/day IV have been used off-label.
-Children
weight 30 kg or less: 3 mg/kg/day IV is the FDA-approved maximum dosage; however, doses up to 4.5 mg/kg/day IV have been used off-label.
weight more than 30 kg: 2.5 mg/kg/day IV (Max: 150 mg) is the FDA-approved maximum dosage; however, doses up to 4.5 mg/kg/day IV (Max: 225 mg/day) have been used off-label.
-Adolescents
weight 30 kg or less: 3 mg/kg/day IV is the FDA-approved maximum dosage; however, doses up to 4.5 mg/kg/day IV have been used off-label.
weight more than 30 kg: 2.5 mg/kg/day IV (Max: 150 mg) is the FDA-approved maximum dosage; however, doses up to 4.5 mg/kg/day IV (Max: 225 mg/day) have been used off-label.

Patients with Hepatic Impairment Dosing
No dosage adjustment is needed in patients with mild, moderate, or severe hepatic impairment.

Patients with Renal Impairment Dosing
No dosage adjustment is needed in patients with renal impairment.

Intermittent and Continuous Hemodialysis
Micafungin is not dialyzable. Supplemental dosing is not required following hemodialysis.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Micafungin prevents the synthesis of an essential fungal cell wall component, beta-1,3-D-glucan, by non-competitively inhibiting beta-1,3-glucan synthase complex. Beta-1,3-D-glucan, which is not present in mammalian cells, interlinks with beta-1,6-D-glucan and chitin to provide fungal cell wall stability. Inhibiting the synthesis of this protein in susceptible yeast (Candida sp.) causes morphological changes to the fungal cell that ultimately result in cell lysis. Some molds (Aspergillus sp.) are also susceptible to decreases in beta-1,3-D-glucan production; however the resulting morphologic changes do not completely inhibit the growth of these fungi as the effects are limited to active cell growth/division of the fungal hyphae. Echinocandins, such as micafungin, inhibit the growth of Candida sp. for more than 12 hours after exposure; however, this post-antifungal effect is less than 0.5 hours for Aspergillus sp.

Micafungin has demonstrated concentration-dependent fungicidal activity against Candida sp. Fungistatic activity has been observed for Aspergillus sp. The Clinical and Laboratory Standards Institute (CLSI) defines MICs for C. albicans, C. krusei, and C. tropicalis as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more. For C. glabrata, the MICs for susceptible, intermediate, and resistant are 0.12 mcg/mL or less, 0.25 mcg/mL, and 0.5 mcg/mL or more, respectively. C. parapsilosis and C. guilliermondii have the highest MIC break-points, susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. For Aspergillus sp., a minimum effective concentration (MEC) is used to determine susceptibility to echinocandins. The MEC is defined as the lowest concentration that results in morphologic changes and is used in place of MIC values because treatment with echinocandins does not completely inhibit growth in Aspergillus sp., making accurate MIC breakpoints difficult to determine. The MEC ranges from 0.015 to 0.25 mcg/mL for Aspergillus sp.

Although rare, echinocandin resistance has been observed among strains of Candida glabrata. Other Candida sp., including C. albicans, C. dubliniensis, C. guilliermondii, C. krusei, C. lusitaniae, C. parapsilosis, and C. tropicalis, have displayed reduced susceptibility to echinocandin therapy resulting from mutations in the fks1 gene, a gene that encodes for the catalytic subunit of beta-1,3-D-glucan synthase complex. The fks1 gene mutation also causes elevations in the MEC of Aspergillus fumigatus; however in Aspergillus sp., reduced susceptibility to echinocandins is thought to result from increased chitin synthesis and mutations in the ecm33 gene. Cross resistance to polyene or the azole antifungals has not been observed.

Pharmacokinetics: Micafungin is administered by intravenous infusion. Micafungin is highly (more than 99%) protein bound, primarily to albumin. At therapeutically relevant concentrations, micafungin does not competitively displace bilirubin binding to albumin. In general, micafungin is widely distributed throughout the body; however, there is poor penetration into urine (less than 2% of a dose) and vitreous humor (less than 1% based on animal data). Micafungin's penetration into the CNS is not fully defined. Data suggest that less than 5% of a dose gets distributed into the cerebrospinal fluid (CSF). Data from an animal model of hematogenous Candida meningoencephalitis which was bridged to neonates using Monte Carlo simulations showed penetration into most CNS compartments, but only at doses more than 2 mg/kg. It was not reliably detected in the CSF. Micafungin's volume of distribution (Vd) in adults is 0.39 +/- 0.11 L/kg. In pediatric patients, it ranges from 0.28 L/kg to 0.51 L/kg, with extremely-low birth weight neonates having the largest Vd. Micafungin metabolism occurs via arylsulfatase to its catechol form (M-1) with further metabolism via catechol-O-methyltransferase (COMT) to its methoxy form (M-2). Micafungin then undergoes further metabolism via hydroxylation by cytochrome P450 isoenzymes to M-5. Even though micafungin is a substrate for and weak inhibitor of CYP3A in vitro, hydroxylation by CYP3A is not a major pathway for micafungin in vivo. Micafungin is neither a substrate nor inhibitor of P-glycoprotein (P-gp) in vitro. Single dose administration of radiolabeled micafungin demonstrated a mean urinary and fecal recovery of 82.5%. Fecal excretion was shown to be the major route of elimination with 71% of the administered dose excreted. The mean elimination half-life of micafungin in adults ranges from 13 to 17.2 hours. In pediatric patients, it ranges from approximately 6.7 to 13.3 hours, with premature neonates typically having the fastest clearance.

Affected cytochrome P450 isoenzymes and drug transporters: none
Micafungin is not a substrate or inhibitor of P-gp and is a poor substrate for CYP450 enzymes. It does not have any significant interaction with the CYP450 enzyme system. In clinical studies, micafungin did not induce the CYP3A4 metabolism of other drugs. Concurrent administration of micafungin and mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, fluconazole, itraconazole, voriconazole, amphotericin B, sirolimus, nifedipine, ritonavir, or rifampin did not alter the pharmacokinetic parameters of micafungin. Furthermore, there was no effect of a single or multiple doses of micafungin on mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, voriconazole, or fluconazole pharmacokinetic parameters.


-Route-Specific Pharmacokinetics
Oral Route
Micafungin has poor oral bioavailability (less than 5%).

Intravenous Route
Micafungin follows a 2-compartment model of distribution; the drug is rapidly distributed to tissues after IV administration. In pediatric patients, exposure (AUC) is linear over the dosage range of 0.5 to 4 mg/kg. Peak concentrations are reached approximately 1 hour after administration.[52970 A loading dose is not required; typically, 85% of the steady-state concentration is achieved after 3 daily doses in adults.


-Special Populations
Pediatrics
Neonates and Infants younger than 4 months
Several pharmacokinetic (PK) trials have been performed in neonates. Calculated PK parameters have varied somewhat among the studies; however, volume of distribution has been higher than that of older populations and clearance has consistently been significantly faster than that of older populations. In general, micafungin clearance is thought to be 3 to 5 times faster in premature neonates compared to in adults. In a pharmacokinetic study of prophylactic micafungin (1 mg/kg/day IV) in 25 premature neonates (gestational age less than 34 weeks; birthweight less than 1.5 kg), mean clearance, volume of distribution, and elimination half-life were 1.48 mL/kg/minute, 0.76 L/kg, and 6.7 hours, respectively. Pharmacokinetic parameters were not significantly different between neonates less than 1 kg (n = 12) and those 1 to 1.5 kg (n = 13). Another study of 12 preterm neonates (median post-conceptional age at enrollment, 28.3 weeks) found no statistical difference in PK parameters in neonates weighing less than 1 kg vs. those weighing 1 kg or more. Exposure data from this study led authors to conclude that a dose of 15 mg/kg given to premature neonates would provide similar systemic exposure as a dose of 5 mg/kg given to an adult. In another PK study in 18 premature neonates (mean gestational age, 26.4 weeks; mean baseline weight, 1.5 kg; mean postnatal age, 5.9 weeks), mean clearance, volume of distribution, and elimination half-life were 0.65 mL/kg/minute, 0.43 L/kg, and 8.3 hours, respectively. Data from the 5 infants weighing 500 g to 1 kg showed a mean clearance and elimination half-life of approximately 1.3 mL/kg/minute and 5.5 hours, respectively. In vitro pharmacokinetic data have shown an 8-fold higher unbound fraction of micafungin in neonatal patients compared with adults. It is postulated that this age-dependent serum protein binding may be responsible for the higher clearance observed in neonates. Micafungin pharmacokinetic data in 103 pediatric patients younger than 4 months of age were assessed using population pharmacokinetics. Predicted micafungin AUC estimates were dose proportional across the dose regimens and age ranges studied. Administration of micafungin 4 mg/kg once daily to pediatric patients younger than 4 months of age produces a mean steady-state AUC of 131 mcg x hour/mL, which is comparable to the steady-state AUC in pediatric patients 4 months of age and older administered micafungin 2 mg/kg/day and adults administered 100 mg once daily.

Infants, Children, and Adolescents 4 months to 17 years
Clearance of micafungin is higher in younger children compared with older children and adolescents; the pharmacokinetic (PK) parameters of micafungin in older children and adolescents are similar to those in adults. In a dose-escalation study in 77 children and adolescents (2 to 17 years), mean clearance (CL) values were 0.385 mL/kg/minute and 0.285 mL/kg/minute for children 2 to 8 years and 9 to 17 years, respectively. Mean corresponding elimination half-lives were 11.6 and 13.3 hours, respectively. Volume of distribution was also greater in the younger children compared with older children and adolescents (0.35 L/kg vs. 0.28 L/kg). Doses studied ranged from 0.5 to 4 mg/kg/dose IV daily. In another PK study in pediatric patients (3 weeks to 15 years), mean CL and elimination half-life were approximately 0.71 mL/kg/minute and 10.1 hours, respectively, for children younger than 5 years (n = 7) and 0.48 mL/kg/minute and 13.8 hours, respectively, for those 5 years and older (n = 5).

Hepatic Impairment
Pharmacokinetic data are not available for pediatric patients with hepatic impairment. In adults with moderate (Child-Pugh score 7 to 9) and severe (Child-Pugh score 10 to 12) hepatic impairment, the Cmax and AUC of micafungin were lowered by approximately 22% and 30%, respectively, compared to values obtained from healthy volunteers. Patients with severe impairment also experienced a mean 2.3-fold increase in the Cmax and AUC of the M-5 metabolite.

Renal Impairment
Pharmacokinetic data are not available for pediatric patients with renal impairment. Adult patients with severe renal dysfunction (CrCl less than 30 mL/minute) achieve similar micafungin exposure as those with normal renal function. Micafungin is not dialyzable.