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  • CLASSES

    Echinocandins Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    Echinocandin antifungal
    Used for Candida infection prophylaxis and treatment
    Efficacy for treatment of infections caused by fungi other than Candida has not been established

    COMMON BRAND NAMES

    Mycamine

    HOW SUPPLIED

    Micafungin Sodium/Mycamine Intravenous Inj Pwd F/Sol: 50mg, 100mg

    DOSAGE & INDICATIONS

    For the treatment of candidemia and invasive candidiasis.
    For the treatment of chronic disseminated (hepatosplenic) candidiasis†.
    Intravenous dosage
    Adults

    100 mg IV once daily for several weeks and followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate.

    Infants, Children, and Adolescents 4 months to 17 years

    2 mg/kg/dose IV once daily (Max: 100 mg/day). If there is an inadequate clinical response after 5 days, may increase dose to 4 mg/kg/day for patients 40 kg or less and 200 mg/day for patients more than 40 kg. Treatment success with micafungin has ranged from 73% to 83%, and efficacy has been comparable to liposomal amphotericin B. Treat for several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate.

    Infants 1 to 3 months

    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 several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate.

    Neonates

    4 mg/kg/dose IV once daily. 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 several weeks, followed by oral fluconazole for patients who are unlikely to have a fluconazole-resistant isolate.

    Intravenous dosage
    Adults

    100 mg IV once daily. Treat for at least 14 days after resolution of symptoms or last positive culture, whichever is longer, for candidemia without metastatic complications. Clinical practice guidelines recommend an echinocandin as initial therapy in both neutropenic and nonneutropenic patients. If the central venous catheter is the presumed source of infection, consider early catheter removal. In addition, all patients should undergo a dilated ophthalmological examination, preferably performed by an ophthalmologist within the first week after diagnosis or recovery from neutropenia.

    Infants, Children, and Adolescents 4 months to 17 years

    2 mg/kg/dose IV once daily (Max: 100 mg/dose). 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%, and efficacy has been comparable to liposomal amphotericin B. Treat for at least 14 days after resolution of symptoms or last positive culture, whichever is longer, for candidemia without metastatic complications. Clinical practice guidelines recommend an echinocandin as initial therapy in both neutropenic and nonneutropenic patients. If the central venous catheter is the presumed source of infection, consider early catheter removal. In addition, all patients should undergo a dilated ophthalmological examination, preferably performed by an ophthalmologist within the first week after diagnosis or recovery from neutropenia.

    Infants 1 to 3 months

    4 mg/kg/dose IV once daily. The FDA-approved labeling states that the safety and efficacy of micafungin 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 at least 14 days after resolution of symptoms or last positive culture, whichever is longer, for candidemia without metastatic complications. Clinical practice guidelines recommend an echinocandin as initial therapy in both neutropenic and nonneutropenic patients. If the central venous catheter is the presumed source of infection, consider early catheter removal. In addition, all patients should undergo a dilated ophthalmological examination, preferably performed by an ophthalmologist within the first week after diagnosis or recovery from neutropenia.

    Neonates

    4 mg/kg/dose IV once daily is the FDA-approved dosage for the treatment of candidemia or invasive candidiasis infections without meningoencephalitis and/or ocular dissemination in infants younger than 4 months. The FDA-approved labeling states that the safety and efficacy of micafungin 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. 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 14 days after resolution of symptoms or last positive culture, whichever is longer, for candidemia without metastatic complications. If the central venous catheter is the presumed source of infection, consider early catheter removal. In addition, all patients should undergo a dilated ophthalmological examination, preferably performed by an ophthalmologist within the first week after diagnosis or recovery from neutropenia.

    For the treatment of esophageal candidiasis.
    Intravenous dosage
    Adults

    150 mg IV once daily. Treat for 14 to 21 days. Recommended as an alternative therapy in patients unable to tolerate oral therapy or those who are refractory to fluconazole. The risk of relapse is greater in HIV-infected patients for esophageal candidiasis and suppressive antifungal therapy may be considered after a course of treatment.

    Children and Adolescents weighing more than 30 kg

    2.5 mg/kg/dose IV (Max: 150 mg/dose) once daily. For HIV-infected adolescents (regardless of weight), 150 mg IV once daily is recommended. Treat for 14 to 21 days; in HIV-infected patients, treat for a minimum of 21 days and for at least 14 days following resolution of symptoms. Recommended as an alternative therapy in patients unable to tolerate oral therapy or those who are refractory to fluconazole.

    Infants and Children 4 months and older weighing 30 kg or less

    3 mg/kg/dose IV once daily. Treat for 14 to 21 days; in HIV-infected patients, treat for a minimum of 21 days and for at least 14 days following resolution of symptoms. Recommended as an alternative therapy in patients unable to tolerate oral therapy or those who are refractory to fluconazole.

    Infants 1 to 3 months†

    Optimal dosing is not well established. 5 to 7 mg/kg/dose IV once daily. Treat for 14 to 21 days; in HIV-infected patients, treat for a minimum of 21 days and for at least 14 days following resolution of symptoms. Recommended as an alternative therapy in patients unable to tolerate oral therapy or those who are refractory to fluconazole.

    For candidiasis prophylaxis in high-risk patients.
    For candidiasis prophylaxis in hematopoietic stem cell transplant recipients.
    Intravenous dosage
    Adults

    50 mg IV once daily. Duration of treatment varied in clinical trials with a mean duration of 19 days (range 6 to 51 days); treatment continued until ANC was at least 500 cells/mm3 or a maximum duration of 42 days after transplantation. Candidiasis prophylaxis is 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.

    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. Candidiasis prophylaxis is 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.

    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. Candidiasis prophylaxis is 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.

    For candidiasis prophylaxis in high-risk intensive care unit patients†.
    Intravenous dosage
    Adults

    100 mg IV once daily. An echinocandin, such as micafungin, is recommended as an alternative therapy to fluconazole for candidiasis prophylaxis in high risk patients in intensive care units with a high rate (more than 5%) of invasive candidiasis.

    For the treatment of invasive aspergillosis† in patients who are refractory to or intolerant of other antifungal therapies.
    Intravenous dosage
    Adults

    100 to 150 mg IV once daily. Clinical practice 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. Clinical practice 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. Clinical practice 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.

    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, clinical practice 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 oropharyngeal candidiasis (thrush)†.
    Intravenous dosage
    Adults

    100 mg IV once daily for 7 to 14 days in patients with azole-refractory disease.

    Children and Adolescents weighing more than 30 kg

    2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 7 to 14 days in patients with azole-refractory disease.[34361] [44913] [52977] [60487]

    Infants and Children 4 months and older weighing 30 kg or less

    3 mg/kg/dose IV once daily for 7 to 14 days in patients with azole-refractory disease.

    Infants 1 to 3 months

    Optimal dosing is not well established. 5 to 7 mg/kg/dose IV once daily for 7 to 14 days in patients with azole-refractory disease.

    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
    Adults

    150 mg IV once daily. 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. 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. 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. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

    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. Treat suppurative thrombophlebitis for at least 2 weeks after candidemia (if present) has cleared.

    For the treatment of Aspergillus cardiovascular system infections†.
    Intravenous dosage
    Adults

    100 to 150 mg IV once daily. Clinical practice 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; longer treatment duration is often necessary. After surgical replacement of an infected valve, consider lifelong antifungal 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. Clinical practice 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; longer treatment duration is often necessary. After surgical replacement of an infected valve, consider lifelong antifungal 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. Clinical practice 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; longer treatment duration is often necessary. After surgical replacement of an infected valve, consider lifelong antifungal therapy.

    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, clinical practice 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; longer treatment duration is often necessary. After surgical replacement of an infected valve, consider lifelong antifungal therapy.

    For the treatment of respiratory infections† (i.e., pneumonia†).
    For the treatment of Candida pneumonia.
    Intravenous dosage
    Adults

    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, 100 mg IV once daily.

    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.

    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.

    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.

    For the treatment of Aspergillus pneumonia.
    Intravenous dosage
    Adults

    100 to 150 mg IV once daily. Clinical practice 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. 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. Clinical practice 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. Clinical practice 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.

    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, clinical practice 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 intraabdominal infections (i.e., peritonitis, intraabdominal abscess), including intraabdominal candidiasis and peritoneal dialysis-related peritonitis†.
    For the treatment of intraabdominal candidiasis.
    Intravenous dosage
    Adults

    100 mg 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.

    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.

    Infants 1 to 3 months

    4 mg/kg/dose IV once daily.

    Neonates

    4 mg/kg/dose IV once daily.

    For the treatment of peritoneal dialysis-related peritonitis†.
    Intravenous dosage
    Adults

    100 to 150 mg IV once daily 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.

    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.

    For the treatment of bone and joint infections†, including osteomyelitis† and infectious arthritis†.
    For the treatment of Candida osteomyelitis or infectious arthritis.
    Intravenous dosage
    Adults

    100 mg IV once daily. 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.

    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.

    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.

    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.

    For the treatment of Aspergillus osteomyelitis or infectious arthritis.
    Intravenous dosage
    Adults

    100 to 150 mg IV once daily. Clinical practice guidelines recommend micafungin as salvage therapy or in settings in which azole and polyene antifungals are contraindicated. Treat for at least 8 weeks; prolonged antifungal therapy (more than 6 months) is frequently necessary. In addition, surgical debridement where feasible is recommended as an adjunct to systemic antifungal 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. Clinical practice guidelines recommend micafungin as salvage therapy or in settings in which azole and polyene antifungals are contraindicated. Treat for at least 8 weeks; prolonged antifungal therapy (more than 6 months) is frequently necessary. In addition, surgical debridement where feasible is recommended as an adjunct to systemic antifungal 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. Clinical practice guidelines recommend micafungin as salvage therapy or in settings in which azole and polyene antifungals are contraindicated. Treat for at least 8 weeks; prolonged antifungal therapy (more than 6 months) is frequently necessary. In addition, surgical debridement where feasible is recommended as an adjunct to systemic antifungal therapy.

    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, clinical practice guidelines recommend micafungin as salvage therapy or in settings in which azole and polyene antifungals are contraindicated. Treat for at least 8 weeks; prolonged antifungal therapy (more than 6 months) is frequently necessary. In addition, surgical debridement where feasible is recommended as an adjunct to systemic antifungal therapy.

    For aspergillosis prophylaxis† in high-risk patients.
    Intravenous dosage
    Adults

    50 to 100 mg IV once daily. Clinical practice guidelines suggest micafungin prophylaxis as an alternative to posaconazole for high-risk patients, including allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) and neutropenic patients with acute myelogenous leukemia or myelodysplastic disease.

    Infants, 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 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. Clinical practice guidelines suggest micafungin prophylaxis as an alternative to posaconazole for high-risk patients, including allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) and neutropenic patients with acute myelogenous leukemia or myelodysplastic disease.

    For the empiric treatment of febrile neutropenia†.
    Intravenous dosage
    Adults

    50 to 150 mg IV once daily. Recommended in patients with persistent or recurrent fever after 4 to 7 days of antibiotics and anticipated neutropenia duration more than 7 days. Aspergillosis clinical practice guidelines recommend 100 mg IV once daily as empiric or preemptive antifungal therapy in allogeneic hematopoietic stem cell transplant recipients and patients treated for acute myelogenous leukemia who remain persistently febrile despite broad-spectrum antibiotic therapy.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    150 mg/day IV.

    Geriatric

    150 mg/day IV.

    Adolescents

    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.
    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.

    Children

    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.
    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.

    Infants

    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.
    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.

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed in patients with mild-to-moderate hepatic impairment. There is no clinical experience in those with severe hepatic impairment (Child-Pugh score > 9, class C).

    Renal Impairment

    No dosage adjustment is needed in patients with renal impairment.
     
    Intermittent hemodialysis
    Micafungin is not dialyzable. Supplemental dosing is not required following hemodialysis.
     
    Continuous hemodialysis
    Micafungin is not dialyzable. Supplemental dosing is not required following hemodialysis.

    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.

    Intravenous Administration

    Reconstitution
    Reconstitute each 50 mg vial or 100 mg vial with 5 mL of either 0.9% Sodium Chloride Injection (without bacteriostatic agent) or 5% Dextrose Injection for a resultant concentration of 10 mg/mL 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
    Adults: Transfer the needed amount of reconstituted micafungin to an IV bag containing 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    Pediatric patients:
    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.
    Discard partially used vials; micafungin is preservative-free.
    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).[44913]
     
    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.[44913]

    STORAGE

    Mycamine:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - See package insert for detailed storage information
    - Store reconstituted product at room temperature (77 degrees F)
    - Store unreconstituted product at 68 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Cholestasis, hepatic disease, hepatitis, jaundice

    Abnormal liver function tests and hyperbilirubinemia have been associated with micafungin administration. Isolated cases of significant hepatic dysfunction, hepatitis, and hepatic failure have been reported. Patients with hepatic disease, jaundice, cholestasis, or hepatitis may have exacerbations of their condition. Also, patients with moderate to severe hepatic impairment (Child-Pugh score 7 or greater) may experience decreased systemic drug exposure.[44913]

    Renal disease, renal failure, renal impairment

    Elevations in serum creatinine and alterations in serum electrolytes have occurred in association with micafungin receipt. Isolated cases of significant renal dysfunction and acute renal failure have been reported. Patients with renal impairment, renal disease, or renal failure may have exacerbations of their condition or electrolyte imbalances.[44913]

    Infants, neonates

    Safety and efficacy of micafungin have not been established for neonates or infants younger than 4 months of age. However, multiple studies have evaluated its use in these populations to treat infections such as candidemia, invasive candidiasis, and invasive aspergillosis. Further, some experts state that if an echinocandin is used in neonates to treat Candida infections, micafungin is the preferred agent. Micafungin has also been used off-label to prevent infections due to Candida or Aspergillus in high-risk infants and neonates (premature neonates, chemotherapy-induced neutropenia, hematopoietic stem cell transplant).

    Pregnancy

    There are no adequate and well-controlled studies evaluating the use of micafungin in human pregnancy to inform a drug-associated risk of adverse developmental outcomes. However, based on animal studies, micafungin may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of micafungin to pregnant rabbits during organogenesis at doses 4 times the maximum recommended human dose resulted in visceral abnormalities and increased abortion. Advise pregnant women of the risk to the fetus if micafungin is used during pregnancy.[44913]

    Breast-feeding

    There are no data available on the presence of micafungin in human milk, the effects on the breast-fed infant, or the effects on milk production. Micafungin was present in the milk of lactating rats after IV administration and it is likely to be present in human milk. Fluconazole may be a potential alternative to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

    Infusion-related reactions

    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-related reactions, infuse solutions with concentrations more than 1.5 mg/mL via a central catheter.

    ADVERSE REACTIONS

    Severe

    oliguria / Early / 23.0-23.0
    GI perforation / Delayed / 0-15.0
    ileus / Delayed / 0-15.0
    pleural effusion / Delayed / 0-15.0
    pancytopenia / Delayed / 0-5.0
    coagulopathy / Delayed / 0-5.0
    intracranial bleeding / Delayed / 0-5.0
    thrombotic thrombocytopenic purpura (TTP) / Delayed / 0-5.0
    anaphylactic shock / Rapid / 0-5.0
    anaphylactoid reactions / Rapid / 0-5.0
    hepatic failure / Delayed / 0-5.0
    hyperkalemia / Delayed / 5.0-5.0
    seizures / Delayed / 0-5.0
    thrombosis / Delayed / 0-5.0
    cardiac arrest / Early / 0-5.0
    myocardial infarction / Delayed / 0-5.0
    pericardial effusion / Delayed / 0-5.0
    atrial fibrillation / Early / 3.0-3.0
    hemolytic anemia / Delayed / Incidence not known
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known

    Moderate

    thrombocytopenia / Delayed / 9.0-75.0
    sinus tachycardia / Rapid / 4.0-26.0
    hypokalemia / Delayed / 0-25.0
    hematuria / Delayed / 4.0-23.0
    phlebitis / Rapid / 19.0-19.0
    elevated hepatic enzymes / Delayed / 3.0-16.0
    infusion-related reactions / Rapid / 0-16.0
    thrombocytosis / Delayed / 0-15.0
    hyperbilirubinemia / Delayed / 0-15.0
    hypocalcemia / Delayed / 0-15.0
    hyperglycemia / Delayed / 0-15.0
    hypermagnesemia / Delayed / 0-15.0
    dehydration / Delayed / 0-15.0
    ascites / Delayed / 0-15.0
    peripheral edema / Delayed / 0-15.0
    hypotension / Rapid / 0-15.0
    edema / Delayed / 0-15.0
    hypertension / Early / 15.0-15.0
    dyspnea / Early / 0-15.0
    hypertonia / Delayed / 0-15.0
    hypoglycemia / Early / 6.0-6.0
    jaundice / Delayed / 0-5.0
    hepatomegaly / Delayed / 0-5.0
    hypernatremia / Delayed / 0-5.0
    delirium / Early / 0-5.0
    encephalopathy / Delayed / 0-5.0
    neutropenia / Delayed / 10.0
    anemia / Delayed / 10.0
    hemolysis / Early / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    hepatitis / Delayed / Incidence not known

    Mild

    diarrhea / Early / 7.0-77.0
    nausea / Early / 7.0-71.0
    vomiting / Early / 7.0-66.0
    fever / Early / 0-61.0
    headache / Early / 9.0-44.0
    insomnia / Early / 37.0-37.0
    abdominal pain / Early / 4.0-35.0
    pruritus / Rapid / 33.0-33.0
    rash / Early / 2.0-30.0
    anxiety / Delayed / 22.0-23.0
    urticaria / Rapid / 0-19.0
    leukocytosis / Delayed / 0-15.0
    epistaxis / Delayed / 9.0-9.0
    injection site reaction / Rapid / Incidence not known

    DRUG INTERACTIONS

    Corticosteroids: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia.
    Cyclosporine: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. In theory, patients who are taking immunosuppressive agents such as cyclosporine concomitantly with micafungin may have additive risks for infection or other side effects. However, the manufacturer has listed no particular precautions for co-use of micafungin with cyclosporine. Concurrent administration of micafungin and cyclosporinel did not alter the pharmacokinetic parameters of micafungin. Furthermore, there was no effect of a single or multiple doses of micafungin on cyclosporine pharmacokinetic parameters.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and antifungals together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Itraconazole: (Moderate) Micafungin was shown to increase the systemic exposure (AUC) of itraconazole by 22% in a pharmacokinetic study. The mechanism of this interaction has not been identified, as micafungin does not significantly affect CYP450 enzymes or P-glycoprotein (P-gp). Itraconazole is not known to alter the pharmacokinetic parameters of micafungin. Patients should be evaluated for itraconazole-related side effects during concurrent therapy; itraconazole dosage adjustment may be necessary.
    Mycophenolate: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. In theory, patients who are taking immunosuppressive agents such as mycophenolate concomitantly with micafungin may have additive risks for infection or other side effects. However, the manufacturer has listed no particular precautions for co-use of micafungin with these medications. Concurrent administration of micafungin and mycophenolate mofetil did not alter the pharmacokinetic parameters of micafungin. Furthermore, there was no effect of a single or multiple doses of micafungin on mycophenolate mofetil pharmacokinetic parameters.
    Nanoparticle Albumin-Bound Sirolimus: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. In theory, patients who are taking immunosuppressive agents such as sirolimus concomitantly with micafungin may have additive risks for infection or other side effects. A pharmacokinetic interaction has been reported, but the mechanism of the interaction is not known, as micafungin does not interfere with CYP450 enzymes and does not inhibit P-glycoprotein (P-gp). During pharmacokinetic study in healthy volunteers, the AUC of sirolimus increased by 21% when coadministered with micafungin. Monitor patients receiving both drugs for possible sirolimus toxicity, and adjust the dose as necessary.
    Nifedipine: (Moderate) Concomitant nifedipine and micafungin administration may increase the systemic exposure and the maximum serum concentration of nifedipine. Nifedipine AUC and Cmax were increased by 18% and 42%, respectively, in the presence of steady-state micafungin compared with nifedipine alone. Patients should be monitored closely for nifedipine-related side effects; nifedipine dosage reduction may be necessary.
    Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the fungal or yeast infection is completely treated.
    Sirolimus: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. In theory, patients who are taking immunosuppressive agents such as sirolimus concomitantly with micafungin may have additive risks for infection or other side effects. A pharmacokinetic interaction has been reported, but the mechanism of the interaction is not known, as micafungin does not interfere with CYP450 enzymes and does not inhibit P-glycoprotein (P-gp). During pharmacokinetic study in healthy volunteers, the AUC of sirolimus increased by 21% when coadministered with micafungin. Monitor patients receiving both drugs for possible sirolimus toxicity, and adjust the dose as necessary.
    Tacrolimus: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. In theory, patients who are taking immunosuppressive agents such as tacrolimus concomitantly with micafungin may have additive risks for infection or other side effects. However, the manufacturer has listed no particular precautions for co-use of micafungin with these medications. Concurrent administration of micafungin and tacrolimus did not alter the pharmacokinetic parameters of micafungin. Furthermore, there was no effect of a single or multiple doses of micafungin on tacrolimus pharmacokinetic parameters

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies evaluating the use of micafungin in human pregnancy to inform a drug-associated risk of adverse developmental outcomes. However, based on animal studies, micafungin may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of micafungin to pregnant rabbits during organogenesis at doses 4 times the maximum recommended human dose resulted in visceral abnormalities and increased abortion. Advise pregnant women of the risk to the fetus if micafungin is used during pregnancy.[44913]

    There are no data available on the presence of micafungin in human milk, the effects on the breast-fed infant, or the effects on milk production. Micafungin was present in the milk of lactating rats after IV administration and it is likely to be present in human milk. Fluconazole may be a potential alternative to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

    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 hour 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. Standardized susceptibility testing methods (broth microdilution technique and disk diffusion technique) are available for Candida sp. Using broth microdilution, the Clinical and Laboratory Standards Institute (CLSI) defines minimum inhibitory concentrations (MICs) for C. albicans, C. krusei, and C. tropicalis as susceptible if 0.25 mcg/mL or less, intermediate if 0.5 mcg/mL, and resistant if 1 mcg/mL or more. For C. glabrata, the MICs for susceptible, intermediate, and resistant are 0.06 mcg/mL or less, 0.12 mcg/mL, and 0.25 mcg/mL or more, respectively. C. parapsilosis has the highest MIC break-points, susceptible if 2 mcg/mL or less, intermediate if 4 mcg/mL, and resistant if 8 mcg/mL or more. For Aspergillus sp., a minimum effective concentration (MEC) is used to determine echinocandin activity. The MEC is defined as the lowest concentration that results in morphologic changes, and ranges from 0.015 to 0.25 mcg/mL.
     
    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.

    Oral Route

    Micafungin has poor oral bioavailability (less than 5%).

    Intravenous Route

    Micafungin follows a 2-compartment model of distribution with exposure (AUC) being linear over the daily dosage range of 50 to 150 mg and 3 to 8 mg/kg. 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. A loading dose is not required; typically, 85% of the steady-state concentration is achieved after 3 daily doses.