Micafungin 50 mg/100 mg Solution

MICAFUNGIN SANDOZ is indicated for:

Adults, adolescents u2265 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/u03bcl) 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/u03bcl) for 10 or more days.

The decision to use MICAFUNGIN SANDOZ should take into account a potential risk for the development of liver tumours. MICAFUNGIN SANDOZ should therefore only be used if other antifungals are not appropriate (see section 4.4).

Posology:

Treatment with MICAFUNGIN SANDOZ should be initiated by a medical practitioner experienced in the management of fungal infections. 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 SANDOZ depends on the body weight of the patient as given in the following table:

*If the patientu2019s 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 u2264 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: For the treatment of oesophageal candidiasis, MICAFUNGIN SANDOZ should be administered for at least one week after resolution of clinical signs and symptoms.
• Prophylaxis of Candida infections: For prophylaxis of Candida infection, MICAFUNGIN SANDOZ should be administered for at least one week after neutrophil recovery.

Experience with MICAFUNGIN SANDOZ in patients less than 2 years of age is limited.

Special populations:

• Use in patients with hepatic impairment: No dose adjustment is necessary in patients with mild or moderate hepatic impairment. There are currently no data available for the use of MICAFUNGIN SANDOZ in patients with severe hepatic impairment and its use is not recommended in these patients (see section 4.4 and 4.8).
• Use in patients with renal impairment: No dose adjustment is necessary in patients with renal impairment.

Method of administration: For intravenous use.

• Hypersensitivity to the active substance micafungin, or to any of the excipients (listed in section 6.1).

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 SANDOZ 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 SANDOZ infusion should be discontinued, and appropriate treatment administered.

Skin reactions: 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 SANDOZ discontinued if lesions progress.

Haemolysis: 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 SANDOZ therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/benefit of continuing MICAFUNGIN SANDOZ therapy.

Renal effects: Micafungin as in MICAFUNGIN SANDOZ may cause kidney problems, renal failure, and abnormal renal function test. Patients should be closely monitored for worsening of renal function.

Co-administration of micafungin as in MICAFUNGIN SANDOZ 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 as in MICAFUNGIN SANDOZ 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).

Lactose content: MICAFUNGIN SANDOZ contains lactose. Patients with the rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take MICAFUNGIN SANDOZ.

Pregnancy: 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. The potential risk for humans is unknown. MICAFUNGIN SANDOZ should not be used during pregnancy.

Breast feeding: It is not known whether micafungin is excreted in human breast milk. Animal studies have shown excretion of micafungin in breast milk. MICAFUNGIN SANDOZ should not be used whilst breast feeding.

Fertility: Testicular toxicity was observed in animal studies. Micafungin as in MICAFUNGIN SANDOZ may have the potential to affect male fertility in humans.

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 as in MICAFUNGIN SANDOZ (see section 4.8).

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, blood alkaline phosphatase increased, phlebitis (primarily in HIV infected patients with peripheral lines), vomiting, and aspartate aminotransferase increased.

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.

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.

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. One case of misdosage of 7.8 mg/kg/day for 7 days was reported in a newborn patient. No adverse reactions associated with this high dose were noted.

There is no experience with overdoses of micafungin as in MICAFUNGIN SANDOZ. In case of overdose, general supportive measures and symptomatic treatment should be administered. Micafungin is highly protein-bound and not dialysable.