Micafungin

Registered South African indications: 

• Invasive candidiasis
• Oesophageal 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

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Male patients of reproductive potential
• Severe hepatic impairment
• Children
• Chronic liver diseases known to represent preneoplastic conditions
• Advanced liver fibrosis
• Cirrhosis
• Viral hepatitis
• Neonatal liver disease
• Congenital liver enzyme defects
• Serious underlying conditions (e.g. advanced AIDS, malignancies) requiring multiple co-medications
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Infections caused by: Candida spp.

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

• IV: See table below; Max: >40kg: 200mg/day; <40kg: 4mg/kg/day

Indication
	> 40kg	<40kg	Treatment duration
Invasive candidiasis	100mg/day	2mg/kg/day	Minimum of 14 days; continue for at least 1 week after two sequential negative blood cultures and post resolution of signs and symptoms
Oesophageal candidiasis	150mg/day	3mg/kg/day	1 week post resolution of signs and symptoms
Prophylaxis of Candida infection - In patients undergoing allogeneic haematopoietic stem cell transplantation - In patients who are expected to have neutropenia for >10 days	50mg/day	1mg/kg/day	1 week after neutrophil recovery

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Infuse over 1 hour

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If the patient's response is inadequate, the dose may be increased to 200 mg/day in patients weighing > 40 kg or 4 mg/kg/day in patients ≤ 40 kg

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See additional prescribing points

Paed. forms avail. in SA and covered in this monograph: inj

Infections caused by: Candida spp.

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Invasive candidiasis

Younger than 4 months (including neonates)

• IV: 4-10mg/kg/day

Between 4 months - 16 years
Weight ≤ 40kg

• IV: 2mg/kg/day

Weight > 40kg

• IV: 100mg/day

Treatment duration: Minimum of 14 days, continue for at least 1 week post resolution of signs and symptoms

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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 should be used due to the dose-dependent penetration of micafungin into the CNS.

Pharmacokinetic data derived from the use of Monte Carlo simulations indicated that a dose range of 9-15 mg/kg/day is appropriate in neonates with CNS infections

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Prophylaxis of Candida infection

- In patients undergoing allogeneic haematopoietic stem cell transplantation
- In patients who are expected to have neutropenia for >10 days

Younger than 4 months (including neonates)

• IV: 2mg/kg/day

Between 4 months - 16 years
Weight ≤ 40kg

• IV: 1mg/kg/day

Weight > 40kg

• IV: 50mg/day

Treatment duration: Continue for at least 1 week after neutrophil recovery

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Infuse over 1 hour

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Treatment should be initiated by a physician experienced in the management of fungal infections

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Experience of use in patients < 2 years is limited

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See additional prescribing points

Pregnancy

• Caution
• 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 should not be used during pregnancy unless clearly necessary

Breastfeeding

• Caution; not recommended
• 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 breastfeeding or to continue/discontinue therapy with micafungin should be made taking into account the benefit of breastfeeding to the child and the benefit of micafungin therapy to the mother

Fertility

• Testicular toxicity was observed in animal studies. Micafungin may have the potential to affect male fertility in humans

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no information available

Elderly            

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Insomnia
• Anxiety
• Confusion
• Headache
• Somnolence
• Tremor
• Dizziness
• Dysgeusia

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Bradycardia
• Phlebitis
• Hypotension
• Hypertension
• Flushing
• Shock

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Dyspepsia
• Constipation

Hepatobiliary Disorders

• Increased blood alkaline phosphatase
• Increased aspartate aminotransferase
• Increased alanine aminotransferase 
• Increased blood bilirubin  
• Abnormal hepatic function tests
• Hepatic failure  
• Increased gamma-glutamyltransferase
• Jaundice
• Cholestasis
• Hepatomegaly
• Hepatitis
• Hepatocellular damage

Genitourinary Disorders

• Increased blood creatinine  
• Increased blood urea  
• Aggravated renal failure
• Renal impairment  
• Acute renal failure

Endocrine and Metabolic Disorders

• Hypokalaemia
• Hyperhidrosis
• Hypomagnesaemia
• Hypocalcaemia
• Hyponatraemia
• Hyperkalaemia
• Hypophosphataemia
• Anorexia

Musculoskeletal Disorders

• Increased blood lactate dehydrogenase

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Pruritus
• Erythema
• Toxic skin eruption
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Injection site thrombosis
• Infusion site inflammation
• Injection site pain
• Peripheral oedema

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reactions
• Anaphylactoid reaction  
• Hypersensitivity
• Leukopenia
• Neutropenia
• Anaemia
• Pancytopenia
• Thrombocytopenia
• Eosinophilia
• Hypoalbuminaemia
• Haemolytic anaemia
• Haemolysis
• Disseminated intravascular coagulation
• Pyrexia
• Rigors

• Hepatotoxic and/or genotoxic agents
• Amphotericin B desoxycholate 
• Sirolimus
• Nifedipine
• Itraconazole

• Hepatic function
• Renal function

 

Considerations for use

• Treatment should be initiated by a physician 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

Hepatic adverse effects

• The decision to use micafungin should take into account a potential risk for the development of liver tumours and should only be used if all other antifungal agents are not appropriate
• 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

Administration directions

• 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
• Micafungin contains no preservatives. 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

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.

Spectrum of activity: Candida spp.

Injection (per vial) 50mg

• Mycamine (Astellas) originator

Injection (per vial) 100mg

• Mycamine (Astellas) originator