Hypersensitivity: During administration of micafungin, anaphylactic/anaphylactoid reactions including shock may occur. If these reactions occur, MYCAMINE should be discontinued and appropriate treatment administered.
Skin and Subcutaneous Tissue Disorders: 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 MYCAMINE discontinued if lesions progress.
Haemolysis: Isolated 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 MYCAMINE therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/benefit of continuing therapy.
Hepatic effects: Liver function should be carefully monitored during MYCAMINE treatment. Early discontinuation in the presence of significant and persistent elevation of ALT/AST is recommended. MYCAMINE 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.
MYCAMINE should only be prescribed after careful benefit-risk assessment and, in particular, taking into consideration the potential risk of liver tumours.
Effects on fertility: Micafungin had no effect on the fertility of male and female rats at doses up to 32 mg/kg/day IV (4-fold the anticipated maximum clinical exposure, based on AUC). However, male rats treated for 9 weeks at 10-32 mg/kg/day IV micafungin (resulting in 1-4-fold the anticipated maximum clinical exposure, based on AUC) showed vacuolation of the epididymal ductal epithelial cells. A dose of 32 mg/kg/day also resulted in higher epididymis weights and reduced numbers of sperm cells. In a 39 week IV study in dogs, seminiferous tubular atrophy and decreased sperm in the epididymis were also observed at 10 and 32 mg/kg/day IV micafungin (resulting in 1-5-fold the anticipated maximum clinical exposure, based on AUC).
Testicular toxicity was observed in two animal species. Although the clinical relevance is unknown, micafungin may have the potential to affect male fertility in humans.
Genotoxicity: Micafungin was not genotoxic nor clastogenic in a standard battery of genotoxicity tests. Micafungin did not induce gene mutations in bacterial assays and did not induce chromosomal aberrations in Chinese Hamster Lung cells in vitro. There was no indication of an induction of micronuclei by micafungin in a micronucleus test in mice or unscheduled DNA synthesis in rat hepatocytes.
Carcinogenicity: No standard carcinogenicity studies have been conducted with micafungin.
Hepatic carcinomas and adenomas were observed in 3 to 6 month repeat dose IV toxicity studies in rats at 32 mg/kg/day (resulting in 4-fold the maximum anticipated clinical exposure, based on AUC) with 12 to 20 month recovery periods. In shorter term studies, altered hepatocellular foci, which were likely precursors to the hepatic tumours, were observed. Exposure at the no observed adverse effect level for altered hepatocellular foci resulted in exposures similar to the maximum anticipated clinically, based on AUC.
It is not known whether the hepatic neoplasms observed in treated rats also occur in other species, or if there is a dose threshold for this effect. The relevance of the hepatocarcinogenic potential of micafungin in humans is unknown.
Effect on laboratory tests: There is no information on the effect of micafungin on laboratory tests.
Use in Pregnancy (Category B31): There are no adequate and well-controlled studies of micafungin in pregnant women.
Micafungin and/or its metabolites were shown to cross the placental barrier and distribute to the foetus in rats. No effects on embryo foetal development were observed in rats given IV doses of micafungin up to 32 mg/kg/day throughout organogenesis (2-3-fold the anticipated maximum clinical exposure, based on AUC). However, treatment of rabbits at doses of 32 mg/kg/day IV (2-fold the maximum anticipated clinical exposure, based on AUC) throughout organogenesis was associated with visceral abnormalities and increased abortion. Visceral abnormalities included abnormal lobation of the lung, levocardia, retrocaval ureter, anomalous right subclavian artery, and dilation of the ureter.
While animal studies are not always predictive of a human response, MYCAMINE should only be used during pregnancy if the potential benefit justifies the potential risk to the foetus.
1 Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is considered uncertain in humans.
Use in Lactation: Micafungin and its metabolites were excreted in the milk of lactating rats. In a pre- and postnatal development study in rats, doses of 32 mg/kg/day IV micafungin (resulting in 2-3-fold the anticipated maximum clinical exposure, based on AUC) were associated with reduced pup birth weights and a possible delay in the time of eyelid opening and balanopreputia cleavage.
It is not known whether micafungin is excreted in human breast milk. Therefore caution should be exercised when MYCAMINE is administered during breastfeeding.
Use in Children: The incidence of some adverse reactions was higher in paediatric patients than in adult patients (see ADVERSE REACTIONS).
Use in Elderly: No dosage adjustment is necessary for the elderly (see PHARMACOLOGY: Pharmacokinetics: Pharmacokinetic characteristics in special populations under Actions).