Mycamine

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ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Mycamine 50 mg powder for concentrate for solution for infusion 
Mycamine 100 mg powder for concentrate for solution for infusion 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Mycamine 50 mg 
 
Each vial contains 50 mg micafungin (as sodium). 
After reconstitution each ml contains 10 mg micafungin (as sodium). 
 
Mycamine 100 mg 
 
Each vial contains 100 mg micafungin (as sodium). 
After reconstitution each ml contains 20 mg micafungin (as sodium). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion 
White compact powder 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Mycamine is indicated for: 
 
Adults, adolescents ≥ 16 years of age and elderly: 
- Treatment of invasive candidiasis. 
- Treatment of oesophageal candidiasis in patients for whom intravenous therapy is appropriate. 
- Prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell 

transplantation or patients who are expected to have neutropenia (absolute neutrophil 
count < 500 cells / µl) for 10 or more days. 

 
Children (including neonates) and adolescents < 16 years of age: 
- Treatment of invasive candidiasis. 
- Prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell 

transplantation or patients who are expected to have neutropenia (absolute neutrophil 
count < 500 cells / µl) for 10 or more days. 

 
The decision to use Mycamine should take into account a potential risk for the development of liver 
tumours (see section 4.4). Mycamine should therefore only be used if other antifungals are not 
appropriate. 
 
Consideration should be given to official/national guidance on the appropriate use of antifungal 
agents. 
 
4.2 Posology and method of administration 
 
Treatment with Mycamine should be initiated by a physician experienced in the management of fungal 
infections. 
 



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Posology 
 
Specimens for fungal culture and other relevant laboratory studies (including histopathology) should 
be obtained prior to therapy to isolate and identify causative organism(s). Therapy may be instituted 
before the results of the cultures and other laboratory studies are known. However, once these results 
become available, antifungal therapy should be adjusted accordingly. 
 
The dose regimen of micafungin depends on the body weight of the patient as given in the following 
tables: 
 
Use in adults, adolescents ≥ 16 years of age and elderly 
 
Indication  
 Body weight > 40 kg Body weight ≤  40 kg 
Treatment of invasive candidiasis 100 mg/day* 2 mg/kg/day* 
Treatment of oesophageal candidiasis  150 mg/day 3 mg/kg/day 
Prophylaxis of Candida infection 50 mg/day 1 mg/kg/day 
*If the patient’s response is inadequate, e.g. persistence of cultures or if clinical condition does not improve, the 
dose may be increased to 200 mg/day in patients weighing > 40 kg or 4 mg/kg/day in patients ≤ 40 kg. 
 
Treatment duration 
Invasive candidiasis: The treatment duration of Candida infection should be a minimum of 14 days. 
The antifungal treatment should continue for at least one week after two sequential negative blood 
cultures have been obtained and after resolution of clinical signs and symptoms of infection. 
 
Oesophageal candidiasis:  Micafungin should be administered for at least one week after resolution of 
clinical signs and symptoms. 
 
Prophylaxis of Candida infections: Micafungin should be administered for at least one week after 
neutrophil recovery. 
 
Use in children ≥ 4 months of age up to adolescents < 16 years of age 
 
Indication  
 Body weight > 40 kg Body weight ≤  40 kg 
Treatment of invasive candidiasis  100 mg/day* 2 mg/kg/day* 
Prophylaxis of Candida infection 50 mg/day 1 mg/kg/day 
*If the patient’s response is inadequate, e.g. persistence of cultures or if clinical condition does not improve, the 
dose may be increased to 200 mg/day in patients weighing > 40 kg or 4 mg/kg/day in patients weighing ≤  40 kg. 
 
Use in children (including neonates) < 4 months of age 
 
Indication  
Treatment of invasive candidiasis 4 -10 mg/kg/day* 
Prophylaxis of Candida infection 2 mg/kg/day 
*Micafungin dosed at 4 mg/kg in children less than 4 months approximates drug exposures achieved in adults 
receiving 100 mg/day for the treatment of invasive candidiasis. If central nervous system (CNS) infection is 
suspected, a higher dosage (e.g. 10 mg/kg) should be used due to the dose-dependent penetration of micafungin 
into the CNS (see section 5.2). 
 
Treatment duration 
Invasive candidiasis: The treatment duration of Candida infection should be a minimum of 14 days. 
The antifungal treatment should continue for at least one week after two sequential negative blood 
cultures have been obtained and after resolution of clinical signs and symptoms of infection. 
 



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Prophylaxis of Candida infections: Micafungin should be administered for at least one week after 
neutrophil recovery. Experience with Mycamine in patients less than 2 years of age is limited. 
 
Hepatic impairment 
No dose adjustment is necessary in patients with mild or moderate hepatic impairment (see section 
5.2). There are currently insufficient data available for the use of micafungin in patients with severe 
hepatic impairment and its use is not recommended in these patients (see sections 4.4 and 5.2). 
 
Renal impairment 
No dose adjustment is necessary in patients with renal impairment (see section 5.2). 
 
Paediatric population 
The safety and efficacy in children (including neonates) less than 4 months of age of doses of 4 and 10 
mg/kg for the treatment of invasive candidiasis with CNS involvement has not been adequately 
established. Currently available data are described in section 4.8, 5.1, 5.2. 
 
Method of administration 
 
For intravenous use. 
After reconstitution and dilution, the solution should be administered by intravenous infusion over 
approximately 1 hour. More rapid infusions may result in more frequent histamine mediated reactions. 
For reconstitution instructions see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to other echinocandins or to any of the excipients listed in 
section 6.1. 
 
4.4 Special warnings and precautions for use 
 

Hepatic effects: 
The development of foci of altered hepatocytes (FAH) and hepatocellular tumours after a 
treatment period of 3 months or longer were observed in rats. The assumed threshold for 
tumour development in rats is approximately in the range of clinical exposure. The clinical 
relevance of this finding is not known. Liver function should be carefully monitored during 
micafungin treatment. To minimise the risk of adaptive regeneration and potentially 
subsequent liver tumour formation, early discontinuation in the presence of significant and 
persistent elevation of ALT/AST is recommended. Micafungin treatment should be 
conducted on a careful risk/benefit basis, particularly in patients having severe liver function 
impairment or chronic liver diseases known to represent preneoplastic conditions, such as 
advanced liver fibrosis, cirrhosis, viral hepatitis, neonatal liver disease or congenital enzyme 
defects, or receiving a concomitant therapy including hepatotoxic and/or genotoxic 
properties. 

 
Micafungin treatment was associated with significant impairment of liver function (increase of ALT, 
AST or total bilirubin > 3 times ULN) in both healthy volunteers and patients. In some patients more 
severe hepatic dysfunction, hepatitis, or hepatic failure including fatal cases have been reported. 
Paediatric patients < 1 year of age might be more prone to liver injury (see section 4.8). 
 
Anaphylactic reactions 
 
During administration of micafungin, anaphylactic/anaphylactoid reactions, including shock, may 
occur. If these reactions occur, micafungin infusion should be discontinued and appropriate treatment 
administered. 
 
Skin reactions 
 



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Exfoliative cutaneous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis 
have been reported. If patients develop a rash they should be monitored closely and micafungin 
discontinued if lesions progress. 
 
Haemolysis 
 
Rare cases of haemolysis, including acute intravascular haemolysis or haemolytic anaemia, have been 
reported in patients treated with micafungin. Patients who develop clinical or laboratory evidence of 
haemolysis during micafungin therapy should be monitored closely for evidence of worsening of these 
conditions and evaluated for the risk/benefit of continuing micafungin therapy. 
 
Renal effects 
 
Micafungin may cause kidney problems, renal failure, and abnormal renal function test. Patients 
should be closely monitored for worsening of renal function. 
 
Interactions with other medicinal products 
 
Co-administration of micafungin and amphotericin B desoxycholate should only be used when the 
benefits clearly outweigh the risks, with close monitoring of amphotericin B desoxycholate toxicities 
(see section 4.5). 
 
Patients receiving sirolimus, nifedipine or itraconazole in combination with micafungin should be 
monitored for sirolimus, nifedipine or itraconazole toxicity and the sirolimus, nifedipine or 
itraconazole dosage should be reduced if necessary (see section 4.5). 
 
Paediatric population 
 
The incidence of some adverse reactions was higher in paediatric patients than in adult patients (see 
section 4.8). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Micafungin has a low potential for interactions with medicines metabolised via CYP3A mediated 
pathways. 
 
Drug interaction studies in healthy human subjects were conducted to evaluate the potential for 
interaction between micafungin and mycophenolate mofetil, ciclosporin, tacrolimus, prednisolone, 
sirolimus, nifedipine, fluconazole, ritonavir, rifampicin, itraconazole, voriconazole and amphotericin 
B. In these studies, no evidence of altered pharmacokinetics of micafungin was observed. No 
micafungin dose adjustments are necessary when these medicines are administered concomitantly. 
Exposure (AUC) of itraconazole, sirolimus and nifedipine was slightly increased in the presence of 
micafungin (22%, 21% and 18% respectively). 
 
Co-administration of micafungin and amphotericin B desoxycholate was associated with a 30% 
increase in amphotericin B desoxycholate exposure. Since this may be of clinical significance this co-
administration should only be used when the benefits clearly outweigh the risks, with close monitoring 
of amphotericin B desoxycholate toxicities (see section 4.4). 
 
Patients receiving sirolimus, nifedipine or itraconazole in combination with micafungin should be 
monitored for sirolimus, nifedipine or itraconazole toxicity and the sirolimus, nifedipine or 
itraconazole dosage should be reduced if necessary (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 



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There are no data from the use of micafungin in pregnant women. In animal studies micafungin 
crossed the placental barrier and reproductive toxicity was seen (see section 5.3). The potential risk for 
humans is unknown. 
Mycamine should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
 
It is not known whether micafungin is excreted in human breast milk. Animal studies have shown 
excretion of micafungin in breast milk. A decision on whether to continue/discontinue breast-feeding 
or to continue/discontinue therapy with Mycamine should be made taking into account the benefit of 
breast-feeding to the child and the benefit of Mycamine therapy to the mother. 
 
Fertility 
 
Testicular toxicity was observed in animal studies (see section 5.3). Micafungin may have the 
potential to affect male fertility in humans. 
 
4.7 Effects on ability to drive and use machines 
 
Micafungin has no or negligible influence on the ability to drive or use machines. However, patients 
should be informed that dizziness has been reported during treatment with micafungin (see section 
4.8). 
 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Based on clinical trial experience, overall 32.2% of the patients experienced adverse drug reactions. 
The most frequently reported adverse reactions were nausea (2.8%), blood alkaline phosphatase 
increased (2.7%), phlebitis (2.5%, primarily in HIV infected patients with peripheral lines), vomiting 
(2.5%), and aspartate aminotransferase increased (2.3%). 
 
Tabulated list of adverse reactions 
 
In the following table adverse reactions are listed by system organ class and MedDRA preferred term. 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

System Organ 
Class 

Common 
≥ 1/100 to < 1/10 

Uncommon 
≥ 1/1,000 to < 1/100 

Rare 
≥ 1/10,000 to 

< 1/1,000 

Not known 
(frequency 
cannot be 

estimated from 
available data) 

Blood and 
lymphatic system 
disorders 

leukopenia, 
neutropenia, anaemia 

pancytopenia, 
thrombocytopenia, 
eosinophilia, 
hypoalbuminaemia 

haemolytic 
anaemia, 
haemolysis 
(see section 
4.4) 

disseminated 
intravascular 
coagulation 

Immune system 
disorders 

 anaphylactic / 
anaphylactoid 
reaction (see section 
4.4), hypersensitivity 

 anaphylactic 
and 
anaphylactoid 
shock (see 
section 4.4) 

Endocrine 
disorders 

 hyperhidrosis   



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System Organ 
Class 

Common 
≥ 1/100 to < 1/10 

Uncommon 
≥ 1/1,000 to < 1/100 

Rare 
≥ 1/10,000 to 

< 1/1,000 

Not known 
(frequency 
cannot be 

estimated from 
available data) 

Metabolism and 
nutritional 
disorders 

hypokalaemia, 
hypomagnesaemia, 
hypocalcaemia 

hyponatraemia, 
hyperkalaemia, 
hypophosphataemia, 
anorexia 

  

Psychiatric 
disorders 

 insomnia, anxiety, 
confusion 

  

Nervous system 
disorders 

headache somnolence, tremor, 
dizziness, dysgeusia 

  

Cardiac disorders  tachycardia, 
palpitations, 
bradycardia 

  

Vascular 
disorders 

phlebitis hypotension, 
hypertension, 
flushing 

 shock 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 dyspnoea   

Gastrointestinal 
disorders 

nausea, vomiting, 
diarrhoea, abdominal 
pain 

dyspepsia, 
constipation 

  

Hepatobiliary 
disorders 

blood alkaline 
phosphatase increased, 
aspartate 
aminotransferase 
increased, alanine 
aminotransferase 
increased, blood 
bilirubin increased 
(including 
hyperbilirubinaemia), 
liver function test 
abnormal 

hepatic failure (see 
section 4.4), gamma-
glutamyltransferase 
increased, jaundice, 
cholestasis, 
hepatomegaly, 
hepatitis 

 hepatocellular 
damage 
including fatal 
cases (see 
section 4.4) 

Skin and 
subcutaneous 
tissue disorders 

rash urticaria, pruritus, 
erythema 

 toxic skin 
eruption, 
erythema 
multiforme, 
Stevens-
Johnson 
syndrome, 
toxic 
epidermal 
necrolysis (see 
section 4.4) 

Renal and urinary 
disorders 

 blood creatinine 
increased, blood urea 
increased, renal 
failure aggravated 

 renal 
impairment 
(see section 
4.4), acute 
renal failure 



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System Organ 
Class 

Common 
≥ 1/100 to < 1/10 

Uncommon 
≥ 1/1,000 to < 1/100 

Rare 
≥ 1/10,000 to 

< 1/1,000 

Not known 
(frequency 
cannot be 

estimated from 
available data) 

General disorders 
and 
administration 
site conditions 

pyrexia, rigors injection site 
thrombosis, infusion 
site inflammation, 
injection site pain, 
peripheral oedema 

  

Investigations  blood lactate 
dehydrogenase 
increased 

  

 
Description of selected adverse reactions 
 
Possible allergic-like symptoms 
Symptoms such as rash and rigors have been reported in clinical studies. The majority were of mild to 
moderate intensity and not treatment limiting. Serious reactions (e.g. anaphylactoid reaction 0.2%, 
6/3028) were uncommonly reported during therapy with micafungin and only in patients with serious 
underlying conditions (e.g. advanced AIDS, malignancies) requiring multiple co-medications. 
 
Hepatic adverse reactions 
The overall incidence of hepatic adverse reactions in the patients treated with micafungin in clinical 
studies was 8.6% (260/3028). The majority of hepatic adverse reactions were mild and moderate. Most 
frequent reactions were increase in AP (2.7%), AST (2.3%), ALT (2.0%), blood bilirubin (1.6%) and 
liver function test abnormal (1.5%). Few patients (1.1%; 0.4% serious) discontinued treatment due to a 
hepatic event. Cases of serious hepatic dysfunction occurred uncommonly (see section 4.4). 
 
Injection-site reactions 
None of the injection-site adverse reactions were treatment limiting. 
 
Paediatric population 
 
The incidence of some adverse reactions (listed in the table below) was higher in paediatric patients 
than in adult patients. Additionally, paediatric patients < 1 year of age experienced about two times 
more often an increase in ALT, AST and AP than older paediatric patients (see section 4.4). The most 
likely reason for these differences were different underlying conditions compared with adults or older 
paediatric patients observed in clinical studies. At the time of entering the study, the proportion of 
paediatric patients with neutropenia was several-fold higher than in adult patients (40.2% and 7.3% of 
children and adults, respectively), as well as allogeneic HSCT (29.4% and 13.4%, respectively) and 
haematological malignancy (29.1% and 8.7%, respectively). 
 
Blood and lymphatic system disorders 
common thrombocytopenia 
 
Cardiac disorders 

 

common tachycardia 
 
Vascular disorders 

 

common hypertension, hypotension 
 
Hepatobiliary disorders 

 

common hyperbilirubinaemia, hepatomegaly 
 
Renal and urinary disorders 

 

common acute renal failure, blood urea increased 



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Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
 
4.9 Overdose 
 
Repeated daily doses up to 8 mg/kg (maximum total dose 896 mg) in adult patients have been 
administered in clinical trials with no reported dose-limiting toxicity. In one spontaneous case, it was 
reported a dosage of 16 mg/kg/day was administered in a newborn patient. No adverse reactions 
associated with this high dose were noted. 
There is no experience with overdoses of micafungin. In case of overdose, general supportive 
measures and symptomatic treatment should be administered. Micafungin is highly protein-bound and 
not dialysable. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antimycotics for systemic use, other antimycotics for systemic use, ATC 
code: J02AX05 
 
Mode of action 
Micafungin non-competitively inhibits the synthesis of 1,3-β-D-glucan, an essential component of the 
fungal cell wall. 1,3-β-D-glucan is not present in mammalian cells. 
Micafungin exhibits fungicidal activity against most Candida species and prominently inhibits 
actively growing hyphae of Aspergillus species. 
 
PK/PD relationship 
 
In animals models of candidiasis, a correlation was observed between exposure of micafungin divided 
by MIC (AUC/MIC) and efficacy defined as the ratio required to prevent progressive fungal growth. A 
ratio of ~2400 and ~1300 was required for C. albicans and C. glabrata, respectively, in these models. 
At the recommended therapeutic dosage of Mycamine, these ratios are achievable for the wild-type 
distribution of Candida spp. 
 
Mechanism(s) of resistance 
 
As for all antimicrobial agents, cases of reduced susceptibility and resistance have been reported and 
cross-resistance with other echinocandins cannot be excluded. Reduced susceptibility to echinocandins 
has been associated with mutations in the Fks1 and Fks2 genes coding for a major subunit of glucan 
synthase. 
 
Breakpoints 
 
EUCAST breakpoints 



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Candida species MIC breakpoint (mg/L) 
≤S (Susceptible) >R (Resistant) 

Candida albicans 0.016 0.016 
Candida glabrata  0.03 0.03 
Candida parapsilosis 0.002 2 
Candida tropicalis 1 Insufficient evidence 
Candida krusei1 Insufficient evidence 
Candida guilliermondii1 Insufficient evidence 
Other Candida spp. Insufficient evidence 
1 MICs for C. tropicalis are 1-2 two-fold dilution steps higher than for C  albicans and C. glabrata. In 
the clinical study, successful outcome was numerically slightly lower for C. tropicalis than for C. 
albicans at both dosages (100 and 150 mg daily). However, the difference was not significant and 
whether it translates into a relevant clinical difference is unknown. MICs for C. krusei are 
approximately 3 two-fold dilution steps higher than those for C. albicans and, similarly, those for C. 
guilliermondii are approximately 8 two-fold dilutions higher. In addition, only a small number of cases 
involved these species in the clinical trials. This means there is insufficient evidence to indicate 
whether the wild-type population of these pathogens can be considered susceptible to micafungin. 
 
Information from clinical studies 
 
Candidaemia and Invasive Candidiasis: Micafungin (100 mg/day or 2 mg/kg/day) was as effective as 
and better tolerated than liposomal amphotericin B (3 mg/kg) as first-line treatment of candidaemia 
and invasive candidiasis in a randomised, double-blind, multinational non-inferiority study. 
Micafungin and liposomal amphotericin B were received for a median duration of 15 days (range, 4 to 
42 days in adults; 12 to 42 days in children). 
Non-inferiority was proven for adult patients, and similar findings were demonstrated for the 
paediatric subpopulations (including neonates and premature infants). Efficacy findings were 
consistent, independent of the infective Candida species, primary site of infection and neutropenic 
status (see Table). Micafungin demonstrated a smaller mean peak decrease in estimated glomerular 
filtration rate during treatment (p<0.001) and a lower incidence of infusion-related reactions (p=0.001) 
than liposomal amphotericin B. 
 

 Overall Treatment Success in the Per Protocol Set, Invasive Candidiasis Study 
 Micafungin Liposomal 

Amphotericin B 
% Difference 

[95% CI]  
N n (%) N n (%)  

Adult Patients 
Overall Treatment Success 202 181 (89.6) 190 170 (89.5) 0.1 [-5.9, 6.1] † 
Overall Treatment Success by Neutropenic Status 
 Neutropenia at baseline 24 18 (75.0) 15 12 (80.0) 0.7 [-5.3, 6.7] ‡ 
 No neutropenia at baseline 178 163 (91.6) 175 158 (90.3) 
Paediatric Patients 
Overall Treatment Success 48 35 (72.9) 50 38 (76.0) -2.7 [-17.3, 11.9] § 
 < 2 years old 26 21 (80.8) 31 24 (77.4) 
 Premature Infants 10 7 (70.0) 9 6 (66.7) 
 Neonates (0 days to 

< 4 weeks) 
7 7 (100) 5 4 (80) 

 2 to 15 years old 22 14 (63.6) 19 14 (73.7) 
Adults and Children Combined, Overall Treatment Success by Candida Species  
Candida albicans 102 91 (89.2) 98 89 (90.8)  
Non-albicans species ¶: all 151 133 (88.1) 140 123 (87.9) 
 C. tropicalis 59 54 (91.5) 51 49 (96.1) 
 C. parapsilosis 48 41 (85.4) 44 35 (79.5) 
 C. glabrata 23 19 (82.6) 17 14 (82.4)  



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 C. krusei 9 8 (88.9) 7 6 (85.7)  
† Micafungin rate minus the liposomal amphotericin B rate, and 2-sided 95% confidence interval for 
the difference in overall success rate based on large sample normal approximation. 
‡ Adjusted for neutropenic status; primary endpoint. 
§ The paediatric population was not sized to test for non-inferiority. 
¶ Clinical efficacy was also observed (< 5 patients) in the following Candida species: C. guilliermondii, C. 
famata, C. lusitaniae, C. utilis, C. inconspicua and C. dubliniensis. 

 
Oesophageal Candidiasis: In a randomised, double-blind study of micafungin versus fluconazole in 
the first-line treatment of oesophageal candidiasis, 518 patients received at least a single dose of study 
drug. The median treatment duration was 14 days and the median average daily dose was 150 mg for 
micafungin (N=260) and 200 mg for fluconazole (N=258). An endoscopic grade of 0 (endoscopic 
cure) at the end of treatment was observed for 87.7% (228/260) and 88.0% (227/258) of patients in the 
micafungin and fluconazole groups, respectively (95% CI for difference: [-5.9%, 5.3%]). The lower 
limit of the 95% CI was above the predefined non-inferiority margin of -10%, proving non-inferiority. 
The nature and incidence of adverse events were similar between treatment groups. 
 
Prophylaxis: Micafungin was more effective than fluconazole in preventing invasive fungal infections 
in a population of patients at high risk of developing a systemic fungal infection (patients undergoing 
haematopoietic stem cell transplantation [HSCT] in a randomised, double-blind, multicentre study). 
Treatment success was defined as the absence of a proven, probable, or suspected systemic fungal 
infection through the end of therapy and absence of a proven or probable systemic fungal infection 
through the end of study. Most patients (97%, N=882) had neutropenia at baseline (< 200 
neutrophils/µL). Neutropenia persisted for a median of 13 days. There was a fixed daily dose of 50 mg 
(1.0 mg/kg) for micafungin and 400 mg (8 mg/kg) for fluconazole. The mean period of treatment was 
19 days for micafungin and 18 days for fluconazole in the adult population (N=798) and 23 days for 
both treatment arms in the paediatric population (N=84). 
The rate of treatment success was statistically significantly higher for micafungin than fluconazole 
(1.6% versus 2.4% breakthrough infections). Breakthrough Aspergillus infections were observed in 1 
versus 7 patients, and proven or probable breakthrough Candida infections were observed in 4 versus 
2 patients in the micafungin and fluconazole groups, respectively. Other breakthrough infections were 
caused by Fusarium (1 and 2 patients, respectively) and Zygomycetes (1 and 0 patients, respectively). 
The nature and incidence of adverse reactions were similar between treatment groups. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Pharmacokinetics are linear over the daily dose range of 12.5 mg to 200 mg and 3 mg/kg to 8 mg/kg. 
There is no evidence of systemic accumulation with repeated administration and steady-state is 
generally reached within 4 to 5 days. 
 
Distribution 
 
Following intravenous administration concentrations of micafungin show a biexponential decline. The 
drug is rapidly distributed into tissues. 
In systemic circulation, micafungin is highly bound to plasma protein (> 99%), primarily to albumin. 
Binding to albumin is independent of micafungin concentration (10-100 µg/ml). 
The volume of distribution at steady state (Vss) was approximately 18-19 litres. 
 
Biotransformation 
 
Unchanged micafungin is the principal circulating compound in systemic circulation. Micafungin has 
been shown to be metabolised to several compounds; of these M-1 (catechol form), M-2 (methoxy 
form of M-1) and M-5 (hydroxylation at the side chain) of micafungin have been detected in systemic 
circulation. Exposure to these metabolites is low and metabolites do not contribute to the overall 
efficacy of micafungin.  



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Even though micafungin is a substrate for CYP3A in vitro, hydroxylation by CYP3A is not a major 
pathway for micafungin metabolism in vivo. 
 
Elimination and excretion 
 
The mean terminal half-life is approximately 10-17 hours and stays consistent across doses up to 
8 mg/kg and after single and repeated administration. Total clearance was 0.15-0.3 ml/min/kg in 
healthy subjects and adult patients and is independent of dose after single and repeated administration. 
Following a single intravenous dose of 14C-micafungin (25 mg) to healthy volunteers, 11.6% of the 
radioactivity was recovered in the urine and 71.0% in the faeces over 28 days. These data indicate that 
elimination of micafungin is primarily non-renal. In plasma, metabolites M-1 and M-2 were detected 
only at trace concentrations and metabolite M-5, the more abundant metabolite, accounted for a total 
of 6.5% relative to parent compound. 
 
Special populations 
 
Paediatric patients: In paediatric patients AUC values were dose proportional over the dose range of 
0.5-4 mg/kg. Clearance was influenced by weight, with mean values of weight-adjusted clearance 1.35 
times higher in the younger children (4 months to 5 years) and 1.14 times higher in paediatric patients 
aged 6 to 11 years. Older children (12-16 years) had mean clearance values similar to those 
determined in adult patients. Mean weight-adjusted clearance in children less than 4 months of age is 
approximately 2.6-fold greater than older children (12-16 years) and 2.3-fold greater than in adults. 
 
PK/PD bridging study demonstrated dose-dependent penetration of micafungin into CNS with the 
minimum AUC of 170 µg*hr/L required to achieve maximum eradication of fungal burden in the CNS 
tissues. Population PK modeling demonstrated that a dose of 10 mg/kg in children less than 4 month 
of age would be sufficient to achieve the target exposure for the treatment of CNS Candida infections. 
 
Elderly: When administered as a single 1-hour infusion of 50 mg the pharmacokinetics of micafungin 
in the elderly (aged 66-78 years) were similar to those in young (20-24 years) subjects. No dose 
adjustment is necessary for the elderly. 
 
Patients with hepatic impairment: In a study performed in patients with moderate hepatic impairment 
(Child-Pugh score 7-9), (n=8), the pharmacokinetics of micafungin did not significantly differ from 
those in healthy subjects (n=8). Therefore, no dose adjustment is necessary for patients with mild to 
moderate hepatic impairment. In a study performed in patients with severe hepatic impairment (Child-
Pugh score 10-12) (n=8), lower plasma concentrations of micafungin and higher plasma 
concentrations of the hydroxide metabolite (M-5) were seen compared to healthy subjects (n=8). 
These data are insufficient to support a dosing recommendation in patients with severe hepatic 
impairment. 
 
Patients with renal impairment: Severe renal impairment (Glomerular Filtration Rate [GFR] < 30 
ml/min) did not significantly affect the pharmacokinetics of micafungin. No dose adjustment is 
necessary for patients with renal impairment. 
 
Gender/Race: Gender and race (Caucasian, Black and Oriental) did not significantly influence the 
pharmacokinetic parameters of micafungin. No dose adjustment of micafungin is required based on 
gender or race. 
 
5.3 Preclinical safety data 
 
The development of foci of altered hepatocytes (FAH) and hepatocellular tumours in rats was 
dependent on both dose and duration of micafungin treatment. FAH recorded after treatment for 13 
weeks or longer persisted after a 13-week withdrawal period and developed into hepatocellular 
tumours following a treatment free period which covered the life span of rats. No standard 
carcinogenicity studies have been conducted but the development of FAH was assessed in female rats 
after up to 20 and 18 months after cessation of a 3 and 6 month treatment, respectively. In both studies 



13 

increased incidences/numbers of hepatocellular tumours were observed after the 18 and 20 month 
treatment free period in the high dose group of 32 mg/kg/day as well as in a lower dose group 
(although not statistically significant). The plasma exposure at the assumed threshold for tumour 
development in rats (i.e. the dose where no FAH and liver tumours were detected) was in the same 
range as the clinical exposure. The relevance of the hepatocarcinogenic potential of micafungin for the 
human therapeutic use is not known. 
 
The toxicology of micafungin following repeated intravenous dosing in rats and/or dogs showed 
adverse responses in liver, urinary tract, red blood cells, and male reproductive organs. The exposure 
levels at which these effects did not occur (NOAEL) were in the same range as the clinical exposure or 
lower. Consequently, the occurrence of these adverse responses may be expected in human clinical use 
of micafungin. 
 
In standard safety pharmacology tests, cardiovascular and histamine releasing effects of micafungin 
were evident and appeared to be time above threshold dependent. Prolongation of infusion time 
reducing the plasma concentration peak appeared to reduce these effects. 
 
In repeated dose toxicity studies in rat signs of hepatotoxicity consisted of increased liver enzymes and 
degenerative changes of hepatocytes which were accompanied by signs of compensatory regeneration. 
In dog, liver effects consisted of increased weight and centrilobular hypertrophy, no degenerative 
changes of hepatocytes were observed. 
 
In rats, vacuolation of the renal pelvic epithelium as well as vacuolation and thickening (hyperplasia) 
of the bladder epithelium were observed in 26-week repeat dose studies. In a second 26-week study 
hyperplasia of transitional cells in the urinary bladder occurred with a much lower incidence. These 
findings showed reversibility over a follow-up period of 18 months. The duration of micafungin 
dosing in these rat studies (6 months) exceeds the usual duration of micafungin dosing in patients (see 
section 5.1). 
 
Micafungin haemolysed rabbit blood in vitro. In rats, signs of haemolytic anaemia were observed after 
repeated bolus injection of micafungin. In repeat dose studies in dogs, haemolytic anaemia was not 
observed. 
 
In reproductive and developmental toxicity studies, reduced birth weight of the pups was noted. One 
abortion occurred in rabbits at 32 mg/kg/day. Male rats treated intravenously for 9 weeks showed 
vacuolation of the epididymal ductal epithelial cells, increased epididymis weights and reduced 
number of sperm cells (by 15%), however, in studies of 13 and 26 weeks duration these changes did 
not occur. In adult dogs, atrophy of seminiferous tubules with vacuolation of the seminiferous 
epithelium and decreased sperm in the epididymides were noted after prolonged treatment (39 weeks) 
but not after 13 weeks of treatment. In juvenile dogs, 39 weeks treatment did not induce lesions in the 
testis and epididymides in a dose dependent manner at the end of treatment but after a treatment free 
period of 13 weeks a dose dependent increase in these lesions were noted in the treated recovery 
groups. No impairment of male or female fertility was observed in the fertility and early embryonic 
development study in rats. 
 
Micafungin was not mutagenic or clastogenic when evaluated in a standard battery of in vitro and in 
vivo tests, including an in vitro study on unscheduled DNA synthesis using rat hepatocytes. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate 
Citric acid anhydrous (to adjust the pH) 
Sodium hydroxide (to adjust the pH) 
 



14 

6.2 Incompatibilities 
 
This medicinal product must not be mixed or co-infused with other medicinal products except those 
mentioned in section 6.6. 
 
6.3 Shelf life 
 
Unopened vial: 3 years. 
 
Reconstituted concentrate in vial 
 
Chemical and physical in-use stability has been demonstrated for up to 48 hours at 25°C when 
reconstituted with sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) 
solution for infusion. 
 
Diluted infusion solution 
 
Chemical and physical in-use stability has been demonstrated for 96 hours at 25°C when protected 
from light when diluted with sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 
50 mg/ml (5%) solution for infusion. 
 
Mycamine contains no preservatives. From a microbiological point of view, the reconstituted and 
diluted solutions should be used immediately. If not used immediately, in-use storage times and 
conditions prior to use are the responsibility of the user and would normally not be longer than 24 
hours at 2 to 8°C, unless the reconstitution and dilution have taken place in controlled and validated 
aseptic conditions. 
 
6.4 Special precautions for storage 
 
Unopened vials 
 
This medicinal product does not require any special storage conditions. 
 
For storage conditions after reconstitution  and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml Type I glass vial with an isobutylene-isoprene (PTFE-laminated) rubber stopper and a flip-off 
cap. The vial is wrapped with an UV-protective film. 
 
Pack size: packs of 1 vial. 
 
6.6 Special precautions for disposal and other handling 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
Mycamine must not be mixed or co-infused with other medicinal products except those mentioned 
below. Using aseptic techniques at room temperature, Mycamine is reconstituted and diluted as 
follows: 
 
1. The plastic cap must be removed from the vial and the stopper disinfected with alcohol. 
2. Five ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) 

solution for infusion (taken from a 100 ml bottle/bag) should be aseptically and slowly injected 
into each vial along the side of the inner wall. Although the concentrate will foam, every effort 
should be made to minimise the amount of foam generated. A sufficient number of vials of 
Mycamine must be reconstituted to obtain the required dose in mg (see table below). 



15 

3. The vial should be rotated gently. DO NOT SHAKE. The powder will dissolve completely. The 
concentrate should be used immediately. The vial is for single use only. Therefore, unused 
reconstituted concentrate must be discarded immediately. 

4. All of the reconstituted concentrate should be withdrawn from each vial and returned into the 
infusion bottle/bag from which it was originally taken. The diluted infusion solution should be 
used immediately. Chemical and physical in-use stability has been demonstrated for 96 hours at 
25°C when protected from light and diluted as described above. 

5. The infusion bottle/bag should be gently inverted to disperse the diluted solution but NOT 
agitated in order to avoid foaming. The solution must not be used if it is cloudy or has 
precipitated. 

6. The infusion bottle/bag containing the diluted infusion solution should be inserted into a 
closable opaque bag for protection from light. 

 
Preparation of the solution for infusion 
 
Dose 
(mg) 

Mycamine vial 
to be used 
(mg/vial) 

Volume of sodium 
chloride (0.9%) or 
glucose (5%) to be 
added per vial 

Volume 
(concentration) 
of reconstituted 
powder 

Standard infusion 
(added up to 
100 ml) 
Final 
concentration 

  50 1 x 50 5 ml approx. 5 ml 
(10 mg/ml) 

0.5 mg/ml 

100 1 x 100 5 ml approx. 5 ml 
(20 mg/ml) 

1.0 mg/ml 

150 1 x 100 + 1 x 
50 

5 ml approx. 10 ml 1.5 mg/ml 

200 2 x 100 5 ml approx. 10 ml 2.0 mg/ml 
 
After reconstitution and dilution, the solution should be administered by intravenous infusion over 
approximately 1 hour. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/08/448/001 
EU/1/08/448/002 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 25 April 2008 
Date of latest renewal: 19 February 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 



16 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



17 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Astellas Ireland Co. Ltd 
Killorglin  
Co. Kerry 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted 
• At the request of the European Medicines Agency.  
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 
• Additional risk minimisation measures 
The MAH shall ensure that prior to prescribing of the product prescribers will receive the 
prescriber checklist. 
 
 
The MAH should agree the final content, format and distribution modalities of the Prescriber 
checklist with the National Competent Authority in each Member State and ensure that the 
materials contain the key elements as described below. 
 
Prescriber checklist 
• The decision to use Mycamine should take into account a potential risk for the development of 

liver tumours. Mycamine should therefore only be used if other antifungals are not appropriate 
• Caution must be demonstrated if the patient: 
 - has severe liver function impairment 
 - has chronic liver diseases known to represent preneoplastic conditions (e.g. advanced liver 

fibrosis, cirrhosis, viral hepatitis, neonatal liver disease or congenital enzyme defects) 
 - is receiving a concomitant therapy including hepatotoxic and/or genotoxic properties 



18 

 
 - has history of haemolysis, haemolytic anaemia or renal impairment. 
• Patients should be carefully monitored for liver damage and for worsening of renal function. 
• To minimise the risk of adaptive regeneration and potentially subsequent liver tumour 

formation, early discontinuation in the presence of significant and persistent elevation of 
ALT/AST is recommended. 

• Patients who develop clinical or laboratory evidence of haemolysis during micafungin therapy 
should be monitored closely for evidence of worsening of these conditions and evaluated for the 
benefit/risk of continuing micafungin therapy. 
 

 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



21 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Mycamine 50 mg powder for concentrate for solution for infusion 
micafungin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains: 50 mg micafungin (as sodium). 
After reconstitution each ml contains 10 mg of micafungin (as sodium). 
 
 
3. LIST OF EXCIPIENTS 
 
Lactose monohydrate, citric acid anhydrous and sodium hydroxide. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



22 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/448/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



23 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Mycamine 50 mg powder for concentrate for solution for infusion 
micafungin 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
50 mg 
 
 
6. OTHER 
 



24 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Mycamine 100 mg powder for concentrate for solution for infusion 
micafungin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains: 100 mg micafungin (as sodium). 
After reconstitution each ml contains 20 mg of micafungin (as sodium). 
 
 
3. LIST OF EXCIPIENTS 
 
Lactose monohydrate, citric acid anhydrous and sodium hydroxide. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



25 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/08/448/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Mycamine 100 mg powder for concentrate for solution for infusion 
micafungin 
Intravenous use. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg 
 
 
6. OTHER 
 



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



28 

Package leaflet: Information for the user 
 

Mycamine 50 mg powder for concentrate for solution for infusion 
Mycamine 100 mg powder for concentrate for solution for infusion 

 
micafungin 

 
Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Mycamine is and what it is used for 
2. What you need to know before you use Mycamine 
3. How to use Mycamine 
4. Possible side effects 
5. How to store Mycamine 
6. Contents of the pack and other information 
 
 
1. What Mycamine is and what it is used for 
 
Mycamine contains the active substance micafungin. Mycamine is called an antifungal medicine 
because it is used to treat infections caused by fungal cells. 
Mycamine is used to treat fungal infections caused by fungal or yeast cells called Candida. Mycamine 
is effective in treating systemic infections (those that have penetrated within the body). It interferes 
with the production of a part of the fungal cell wall. An intact cell wall is necessary for the fungus to 
continue living and growing. Mycamine causes defects in the fungal cell wall, making the fungus 
unable to live and grow. 
 
Your doctor has prescribed Mycamine for you in the following circumstances when there are no other 
suitable antifungal treatments available (see section 2): 
 
• To treat adults, adolescents and children including neonates who have a serious fungal infection 

called invasive candidiasis (infection that has penetrated the body). 
• To treat adults and adolescents ≥ 16 years of age who have a fungal infection in the gullet 

(oesophagus) where treatment into a vein (intravenous) is appropriate. 
• To prevent infection with Candida in patients who are having a bone-marrow transplant or who 

are expected to have a neutropenia (low levels of neutrophils, a type of white blood cell) for 10 
days or more. 

 
 
2. What you need to know before you use Mycamine 
 
Do not use Mycamine 
- if you are allergic  to micafungin, other echinocandins (Ecalta or Cancidas) or any of the other 

ingredients of this medicine (listed in section 6). 
 
Warnings and precautions 
In rats, long-term treatment with micafungin led to liver damage and subsequent liver tumours. The 
potential risk of developing liver tumours in humans is not known, and your doctor will assess the 
benefits and risks of Mycamine treatment before starting your medicine. Please tell your doctor if you 
have severe liver problems (e.g. liver failure or hepatitis) or have had abnormal liver function tests. 
During treatment your liver functions will be monitored more closely. 



29 

 
Talk to your doctor or pharmacist before using Mycamine 
- if you are allergic to any medicine 
- if you have haemolytic anaemia (anaemia due to breakdown of red blood cells) or haemolysis 

(breakdown of red blood cells). 
- if you have kidney problems (e.g. kidney failure and abnormal kidney function test). If this 

happens, your doctor may decide to monitor your kidney function more closely. 
 
Micafungin may also cause severe inflammation/eruption of the skin and mucous membranes 
(Stevens-Johnson syndrome, toxic epidermal necrolysis). 
 
Other medicines and Mycamine 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
It is especially important to inform your doctor if you are using amphotericin B desoxycholate or 
itraconazole (antifungal antibiotics), sirolimus (an immunosuppressant) or nifedipine (calcium channel 
blocker used to treat high blood pressure). Your doctor may decide to adjust the dose of these 
medicines. 
 
Mycamine with food and drink 
As Mycamine is given intravenously (into a vein), no restrictions on food or drink are required. 
 
Pregnancy and breast-feeding 
If you are pregnant of breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
Mycamine should not be used during pregnancy unless clearly necessary. If you use Mycamine you 
should not breast-feed. 
 
Driving and using machines 
Micafungin is unlikely to have an effect on driving or using machines. However some people may feel 
dizzy when taking this medicine and if this happens to you, do not drive or use any tools or machines. 
Please inform your doctor if you experience any effects that may cause you to have problems with 
driving or using other machinery. 
 
Mycamine contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-
free’. 
 
 
3. How to use Mycamine 
 
Mycamine must be prepared and given to you by a doctor or another healthcare professional. 
Mycamine should be administered once daily by slow intravenous (into a vein) infusion. Your doctor 
will determine how much Mycamine you will receive each day.  
 
Use in adults, adolescents ≥ 16 years of age and elderly 
- The usual dose to treat an invasive Candida infection is 100 mg per day for patients weighing 

40 kg or more and 2 mg/kg per day for patients weighing 40 kg or less. 
- The dose to treat a Candida infection of the oesophagus is 150 mg for patients weighing more 

than 40 kg and 3 mg/kg per day for patients weighing 40 kg or less. 
- The usual dose to prevent invasive Candida infections is 50 mg per day for patients weighing 

more than 40 kg and 1 mg/kg per day for patients weighing 40 kg or less. 
 
Use in children > 4 months of age and adolescents < 16 years of age 
- The usual dose to treat an invasive Candida infection is 100 mg per day for patients weighing 

40 kg or more and 2 mg/kg per day for patients weighing 40 kg or less. 



30 

- The usual dose to prevent invasive Candida infections is 50 mg per day for patients weighing 
more than 40 kg and 1 mg/kg per day for patients weighing 40 kg or less. 
 

Use in children and newborns < 4 months of age 
- The usual dose to treat an invasive Candida infection is 4-10 mg/kg per day. 
- The usual dose to prevent invasive Candida infections is 2 mg/kg per day. 
 
If you receive 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. 
 
If you miss a dose of 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. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If you experience an allergic attack, or a severe skin reaction (e.g. blistering and peeling of the skin), 
you must inform your doctor or nurse immediately 
 
Mycamine may cause the following other side effects: 
 
Common (may affect up to 1 in 10 people) 
- abnormal blood tests (decreased white blood cells [leucopenia; neutropenia]); decreased red 

blood cells (anaemia) 
- decreased potassium in the blood (hypokalaemia); decreased magnesium in the blood 

(hypomagnesaemia); decreased calcium in the blood (hypocalcaemia) 
- headache 
- inflammation of the vein wall (at injection-site) 
- nausea (feeling sick); vomiting (being sick); diarrhoea; abdominal pain 
- abnormal liver function tests (increased alkaline phosphatase; increased aspartate 

aminotransferase, increased alanine aminotransferase) 
- increased bile pigment in the blood (hyperbilirubinaemia) 
- rash 
- fever 
- rigors (shivering) 
 
Uncommon (may affect up to 1 in 100 people) 
- abnormal blood tests (decreased blood cells [pancytopenia]); decreased blood platelets 

(thrombocytopenia); increases in a certain type of white blood cells called eosinophils; 
decreased albumin in the blood (hypoalbuminaemia) 

- hypersensitivity 
- increased sweating 
- decreased sodium in the blood (hyponatraemia); increased potassium in the blood 

(hyperkalaemia); decreased phosphates in the blood (hypophosphataemia); anorexia (eating 
disorder) 

- insomnia (difficulty in sleeping); anxiety; confusion 
- feeling lethargic (somnolence); trembling; dizziness; disturbed taste 
- increased heart rate; stronger heartbeat; irregular heartbeat 
- high or low blood pressure; skin flushing 



31 

- shortness of breath 
- indigestion; constipation 
- liver failure; increased liver enzymes (gamma-glutamyltransferase); jaundice (yellowing of the 

skin or whites of the eyes caused by liver or blood problems); reduced bile reaching the intestine 
(cholestasis); enlarged liver; liver inflammation 

- itchy rash (urticaria); itching; skin flushing (erythema) 
- abnormal kidney function tests (increased blood creatinine; increased urea in the blood); 

aggravated kidney failure 
- increase in an enzyme called lactate dehydrogenase 
- clotting in vein at injection-site; inflammation at injection-site; pain at injection-site; collection 

of fluid in your body 
 
Rare (may affect up to 1 in 1,000 people) 
- anaemia due to breakdown of red blood cells (haemolytic anaemia), breakdown of red blood 

cells (haemolysis) 
 
Not known (frequency cannot be estimated from the available data) 
- disorder of blood clotting system 
- (allergic) shock 
- damage to liver cells including death 
- kidney problems; acute kidney failure 
 
Additional side effects in children and adolescents 
The following reactions have been reported more often in paediatric patients than in adult patients: 
Common (may affect up to 1 in 10 people) 
- decreased blood platelets (thrombocytopenia) 
- increased heart rate (tachycardia) 
- high or low blood pressure 
- increased bile pigment in the blood (hyperbilirubinaemia); enlarged liver 
- acute kidney failure; increased urea in the blood 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Mycamine 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use Mycamine after the expiry date which is stated on the vial and on the carton. The expiry 
date refers to the last day of that month. 
 
The unopened vial does not require any special storage conditions.  
The reconstituted concentrate and the diluted infusion solution should be used immediately, because it 
does not contain any preservatives to prevent bacterial contamination. Only a trained healthcare 
professional who has read the complete directions properly can prepare this medicine for use. 
 
Do not use the diluted infusion solution if it is cloudy or precipitated. 
 
In order to protect the infusion bottle / bag containing the diluted infusion solution from light it should 
be inserted into a closable opaque bag. 
 
The vial is for single use only. Therefore, please discard unused reconstituted concentrate 
immediately. 



32 

 
 
 
 
6. Contents of the pack and other information 
 
What Mycamine contains 
 
- The active substance is micafungin (as sodium). 

1 vial contains 50 mg or 100 mg micafungin (as sodium). 
- The other ingredients are lactose monohydrate, citric acid anhydrous and sodium hydroxide. 
 
What Mycamine looks like and contents of the pack 
 
Mycamine 50 mg or 100 mg powder for concentrate for solution for infusion is a white compact 
freeze-dried powder. Mycamine is supplied in a box containing 1 vial. 
 
Marketing Authorisation Holder 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
Netherlands 
 
Manufacturer 
Astellas Ireland Co., Ltd. 
Killorglin, County Kerry 
Ireland 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder: 
 
België/Belgique/Belgien 
Astellas Pharma B.V. Branch 
Tél/Tel: +32 (0)2 5580710 

Lietuva 
Biocodex UAB 
Tel: +370 37 408 681 

 
България 
Астелас Фарма ЕООД 
Teл.: +359 2 862 53 72 
 

 
Luxembourg/Luxemburg 
Astellas Pharma B.V. Branch 
Belgique/Belgien 
Tél/Tel: +32 (0)2 5580710 
 

Česká republika 
Astellas Pharma s.r.o. 
Tel: +420 221 401 500 
 

Magyarország 
Astellas Pharma Kft. 
Tel: +36 1577 8200 
 

Danmark 
Astellas Pharma a/s 
Tlf: +45 43430355 
 

Malta 
Astellas Pharmaceuticals AEBE 
Greece 
Τel: +30 210 8189900 
 

Deutschland 
Astellas Pharma GmbH 
Tel: +49 (0)89 454401 
 

Nederland 
Astellas Pharma B.V. 
Tel: +31 (0)71 5455745 

Eesti 
Biocodex OÜ 
Tel: +372 6 056 014 

Norge 
Astellas Pharma 
Tlf: +47 6676 4600 
 



33 

 
Ελλάδα 
Astellas Pharmaceuticals AEBE 
Tηλ: +30 210 8189900 

Österreich 
Astellas Pharma Ges.m.b.H. 
Tel: +43 (0)1 8772668 
 

España 
Astellas Pharma S.A. 
Tel: +34 91 4952700 
 

Polska 
Astellas Pharma Sp.z o.o. 
Tel.: +48 225451 111 
 

France 
Astellas Pharma S.A.S. 
Tél: +33 (0)1 55917500 
 

Portugal 
Astellas Farma, Lda. 
Tel: +351 21 4401320 
 

Hrvatska 
Astellas d.o.o. 
Tel: + 385 1 670 01 02 

România 
S.C.Astellas Pharma SRL 
Tel: +40 (0)21 361 04 95/96/92 
 

Ireland 
Astellas Pharma Co. Ltd. 
Tel: +353 (0)1 4671555 
 

Slovenija 
Astellas Pharma d.o.o. 
Tel: +386 (0) 14011 400 

 
Ísland 
Vistor hf. 
Tel: +354 535 7000 
 

Slovenská republika 
Astellas Pharma s.r.o., organizačná zložka 
Tel: +421 2 4444 2157 

Italia 
Astellas Pharma S.p.A. 
Tel: +39 02 921381 
 

Suomi/Finland 
Astellas Pharma 
Puh/Tel: +358 (0)9 85606000 

Κύπρος 
Astellas Pharmaceuticals AEBE 
Ελλάδα 
Tηλ: +30 210 8189900 
 

Sverige 
Astellas Pharma AB 
Tel: +46 (0)40-650 15 00 

Latvija 
Biocodex SIA 
Tel: +371 67 619365 

United Kingdom 
Astellas Pharma Ltd. 
Tel: +44 (0) 203 3798700 
 

 
  
 
 
This leaflet was last approved in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 
 
--------------------------------------------------------------------------------------------------------------------------- 



34 

The following information is intended for medical or healthcare professionals only: 
 
Mycamine must not be mixed or co-infused with other medicinal products except those mentioned 
below. Using aseptic techniques at room temperature, Mycamine is reconstituted and diluted as 
follows: 
 
1. The plastic cap must be removed from the vial and the stopper disinfected with alcohol. 
2. Five ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) 

solution for infusion (taken from a 100 ml bottle/bag) should be aseptically and slowly injected 
into each vial along the side of the inner wall. Although the concentrate will foam, every effort 
should be made to minimise the amount of foam generated. A sufficient number of vials of 
Mycamine must be reconstituted to obtain the required dose in mg (see table below). 

3. The vial should be rotated gently. DO NOT SHAKE. The powder will dissolve completely. The 
concentrate should be used immediately. The vial is for single use only. Therefore, unused 
reconstituted concentrate must be discarded immediately. 

4. All of the reconstituted concentrate should be withdrawn from each vial and returned into the 
infusion bottle/bag from which it was originally taken. The diluted infusion solution should be 
used immediately. Chemical and physical in-use stability have been demonstrated for 96 hours 
at 25°C when protected from light and diluted as described above. 

5. The infusion bottle/bag should be gently inverted to disperse the diluted solution but NOT 
agitated in order to avoid foaming. The solution must not be used if it is cloudy or has 
precipitated. 

6. The infusion bottle/bag containing the diluted infusion solution should be inserted into a 
closable opaque bag for protection from light. 

 
Preparation of the solution for infusion 
 

Dose 
(mg) 

Mycamine vial 
to be used 
(mg/vial) 

Volume of sodium 
chloride (0.9%) or 
glucose (5%) to be 
added per vial 

Volume 
(concentration) 
of reconstituted 
powder 

Standard infusion 
(added up to 
100 ml) 
Final 
concentration 

  50 1 x 50 5 ml approx. 5 ml 
(10 mg/ml) 

0.5 mg/ml 

100 1 x 100 5 ml approx. 5 ml 
(20 mg/ml) 

1.0 mg/ml 

150 1 x 100 + 1 x 
50 

5 ml approx. 10 ml 1.5 mg/ml 

200 2 x 100 5 ml approx. 10 ml 2.0 mg/ml 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET