Pharmacotherapeutic group:

Micafungin is a broad spectrum antifungal agent originally developed by Astellas Pharmaceutical Inc. Japan which belongs to the echinocandin class. It has a significant activity against Candida sp., and Aspergillus sp. the main causative fungi of deep seated mycosis. Micafungin exhibits potent in vitro activity against Candida sp. that are resistant to fluconazole or itraconazole. Micafungin is fungicidal against Candida sp. and inhibits germination and hyphal extension in Aspergillus sp. Micafungin also has potent protective or therapeutic effect against disseminated candidiasis, oral and esophageal candidiasis, disseminated aspergillosis and pulmonary aspergillosis.

Mechanism of action: Micafungin non-competitively inhibits biosynthesis of 1,3-ß-D- glucan which is an essential component of fungal cell walls.

Therapeutic indications:

Mycamine is indicated for the treatment of the following infections caused by Aspergillus sp. and Candida sp.: Fungemia, respiratory mycosis, gastrointestinal mycosis. Prophylaxis of Aspergillus and Candida infections in patients undergoing hematopoietic stem cell transplantation (HSCT).

a.       Do not take Mycamine

If you are hypersensitive to micafungin, to other echinocandins or any of the other ingredients of Mycamine.

b.       Take special care with Mycamine

•  Micafungin sodium should be administered with care in the following patients:

1-   Patients with a history of hypersensitivity to drugs

2-   Patients with hepatic impairment (Administration of micafungin sodium may aggravate hepatic impairment.)

•  Important Precautions:

1.  Patients should be monitored carefully by conducting periodic liver function tests, etc. If any abnormalities are observed, appropriate measures, such as discontinuation of the product, should be taken. In addition, animal studies have shown that this product induces altered hepatocellular foci, some of which later formed tumors. See ”Other Clinically Significant Adverse Reactions”.

2.  Clinical studies have showed that hepatic function disorder occurred more frequently in children than in adults. Therefore careful attention should be paid when administering micafungin sodium to children.

3.  If aspergillosis or candidiasis develops after the start of prophylaxis with micafungin sodium, patients should not continue administration and appropriate measures, such as switching or other products or increasing the dose should be taken.

4.   When it becomes clear that the causative organism is not Aspergillus sp. or candida sp., or whenit becomes clear that micafungin sodium is not effective, , appropriate measures such as switching to other products should be taken.

5.   The duration of treatment with this drug should be limited to the minimum required for treatment of the disease.

Aspergillosis and candidiasis (adults):

1-               As the safety of this product in increased doses up to 300 mg daily for severe or refractory infections has not been fully established, the product at these dose levels should be administered with caution such as close observation of the patient’s condition

2-          For patients who weigh 50 kg or less, the dosage should not exceed 6 mg kg body weight daily.

Prophylaxis of Aspergillus and Candida infections in pa-tients undergoing hematopoietic stem cell transplantation (adults):

1-  Treatment with this product should be stopped when appropriate, such as when the neutrophil count re-covers to ≥500/mm3

2- For patients who weigh 50 kg or less, the dosage should not exceed 1 mg (potency)/kg body weight daily.

Aspergillosis and candidiasis (children):

1-  As the safety of this product in increased doses up to 6 mg (potency)/kg daily for severe or refractory in-fections has not been fully established, precautions, such as close observation of the patient’s condition, should be taken when administering the product at these dose levels [clinical experience with doses of 6 mg (potency)/kg daily is limited both in Japan and other countries.)].

2-    For patients who weigh 50 kg or more, the dosage should not exceed 300 mg (potency) daily.

Prophylaxis of Aspergillus and Candida infections in pa-tients undergoing hematopoietic stem cell transplantation (children):

1-  Treatment with this product should be stopped when appropriate, such as when the neutrophil count re-covers to ≥500/mm3

2- For patients who weigh 50 kg or more, the dosage should not exceed 50 mg (potency) daily.

c.       Taking other medicines, herbal or dietary supplements

Micafungin has a low potential for interactions with medicines metabolised via CYP3A mediated pathways.

Exposure (AUC) of sirolimus was increased in the presence of micafungin (21%). Patients receiving sirolimus in combination with micafungin should be monitored for sirolimus toxicity and the sirolimus dosage should be adjusted if necessary.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

d.       Using Mycamine with food and drink

Not applicable

e.       Pregnancy and breast-feeding

Pregnancy: The safety of Micafungin sodium in pregnant women has not been established. Micafungin sodium should be administered in pregnant women or women who may possibly be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment.

Breast-feeding: In animal studies, micafungin sodium was found to be excreted in breast milk. Therefore, it is advisable to avoid using micafungin sodium in lactating mothers. If use of micafungin sodium is judged to be essential, breast feeding must be discontinued during treatment.

Ask your doctor or pharmacist for advice before taking any medicine.

f.        Driving and using machines

Not applicable

g.       Important information about some of the ingredients of Mycamine

Not applicable

1.      Adults Aspergillosis:

For adults, the usual single daily dose is 50 – 150 mg of micafungin sodium infused intravenously once daily. The dosage can be increased according to the patient’s condition for severe or refractory aspergillosis up to 300 mg / day.

Candidiasis:

For adults, the usual single daily dose is 50 mg of micafungin sodium infused intravenously once daily. The dosage can be increased according to the patient’s condition for severe or refractory candidiasis up to 300 mg /day.

Prophylaxis of Aspergillus and Candida Infections in patients undergoing HSCT:  For adults, the usually single daily dose is 50 mg of micafungin sodium infused intravenously once daily.

2.      Children Aspergillosis:

For children, the usual single daily dose is 1 – 3 mg /kg body weight of micafungin sodium. This product should be infused intravenously once daily. The dosage can be increased according to the patient’s condition for severe or refractory aspergillosis up to 6 mg /kg daily.

Candidiasis:

For children, the usual single daily dose is 1 mg /kg of micafungin sodium. This product should be infused intravenously once daily. The dosage can be in-creased according to the patient’s condition for severe or refractory candidiasis up to 6 mg /kg daily.

Prophylaxis of Aspergillus and Candida infections in patients undergoing HSCT:

For children, the single daily dose is 1 mg /kg of micafungin sodium. This product should be infused intravenously once daily.

The safety of this product in low birth weight infants and neonates has not been established. In clinical studies, the plasma drug concentration tended to be lower in low birth weight infants. Since clinical studies showed that hepatic function disorder occurred more frequently in children then in adults, great care should be taken when administering this product to children.

3.      Use in the Elderly

Since elderly patients often have reduced physiological function, dosage should be carefully determined and other appropriate measures should be considered.

a.       If you use more Mycamine than you should

Your doctor monitors your response and condition to determine what dose of Mycamine is needed. However, if you are concerned that you may have been given too much Mycamine, speak to your doctor or another healthcare professional immediately.

b.       If you forget to use Mycamine

Your doctor monitors your response and condition to determine what Mycamine treatment is needed. However, if you are concerned that you may have missed a dose, speak to your doctor or another healthcare professional immediately.

c.       If you stop using Mycamine Not applicable.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

a-                    Clinically significant adverse reactions

Hematologic disorder: Leukopenia (incidence unknown*), neutropenia (incidence 1.1%), hemolytic anemia (including intravascular hemolysis; incidence unknown*), disseminated intravascular coagulation (incidence unknown) or thrombocytopenia may occur. Patients should be carefully monitored by periodic examination, etc. and appropriate measures such as discontinuation of treatment should be taken if such abnormalities are observed. In addition, haemolytic anemia may occur immediately after administration of this product, therefore appropriate measures, such as discontinuation of treatment, should be taken if hemolysis is observed.

Shock, anaphylactoid reactions: Shock or anaphylactoid reactions (incidence unknown*) may occur. Patients should be carefully monitored and if abnormalities such as decreased blood pressure, oral cavity discomfort, dyspnea, generalized flushing, angioedema, or urticaria, etc. are observed, this product should be discontinued, and if necessary, appropriate measures such as maintenance of the airway or administration of adrenaline, steroids or antihistamines, etc. should be taken.

Hepatic function disorder or jaundice: Hepatic function disorder with increased AST (GOT), ALT (GPT), gamma GT or ALP, etc., or jaundice may occur (incidence unknown*). Patients should be carefully monitored by periodic examination, etc. and appropriate measures such as discontinuation of treatment should be taken if such abnormalities are observed.

Acute renal failure: Serious renal disorder such as acute renal failure may occur (incidence unknown*). Patients should be carefully monitored by periodic examination, etc. and appropriate measures such as discontinuation of treatment should be taken if such abnormalities are observed.

Toxic epidermal necrolysis (TEN), oculomucocutaneous syndrome (Stevens-Johnson syndrome), erythema multiforme: Since toxic epidermal necrolysis, oculomucocutaneous syndrome, erythema mul-tiforme (incidence unknown*, each) may occur, patients should be observed carefully. If any abnormalities are observed during treatment, appropriate measures such as discontinuation of this product should be taken.

*Incidence unknown: incidence is not calculated because of spontaneous reports.

b-                   Other adverse reactions

Note: In case of occurrence of any serious adverse effects related to the use of this product, please contact Hikma Pharmaceuticals.

Store below 30ºC, away from light.

The reconstituted product may be stored in the original vial for up to 24 hours at room temperature, 25° C (77° F).

The diluted infusion should be protected from light and may be stored for up to 24 hours at room temperature, 25° C (77° F).

Keep medicament out of the reach of children