Drugs List

Therapeutic Indications

Uses

Candidal infection of the oesophagus: treatment
Prophylaxis of candida infection in haematopoietic stem cell transplant pts
Prophylaxis of candidiasis in pts expected to have neutropenia for 10+ days
Systemic candidiasis

Adults, elderly and adolescents aged 16 years or over

Treatment of invasive candidiasis.

Treatment of oesophageal candidiasis where intravenous therapy is appropriate.

Prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation.

Prophylaxis of Candida infection in patients expected to have neutropenia (absolute neutrophil count under 500 cells/microlitre) for 10 or more days.

Children aged under 16 years of age (including neonates)

Treatment of invasive candidiasis.

Prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation.

Prophylaxis of Candida infection in patients expected to have neutropenia (absolute neutrophil count under 500 cells/microlitre) for 10 or more days.

Micafungin should only be used where other antifungals are not appropriate. The decision to use micafungin should take into account the risk of liver tumour development.

Administration

For intravenous infusion after reconstitution and dilution.

The infusion should be administered over one hour. More rapid infusions increase the risk of histamine mediated reactions.

Contraindications

Breastfeeding
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Children under 2 years
Chronic hepatic disorder
Extensive hepatic fibrosis
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatitis
Hereditary fructose intolerance
Lactose intolerance
Renal impairment

Advise patient ability to drive or operate machinery may be impaired
Consult national/regional policy on the use of anti-infectives
Treatment to be initiated and supervised by a specialist
Some formulations contain lactose
Some formulations contain sucrose
Monitor hepatic function
Monitor patient closely for haemolysis
Monitor renal function
Advise patients to report any unusual rash to the prescriber
May cause anaphylactic / anaphylactoid reactions
May induce or enhance hepatic tumour development
Discontinue if anaphylactoid reaction occurs
Discontinue if significant/persistent hepatic function abnormalities occur
Discontinue treatment if progressive skin rash occurs
Not licensed for all indications in all age groups
Male: May cause infertility

In studies with rats, the development of foci of altered hepatocytes and hepatocellular tumours were observed after a treatment period of 3 months or longer. The assumed threshold for tumour development in rats is approximately in the range of clinical exposure. The risk of these effects in humans cannot be excluded. Hepatic function should be carefully monitored during micafungin therapy. To reduce the risk of adaptive regeneration and potential hepatic tumour formation, the discontinuation of micafungin when ALT/AST levels are significantly and persistently elevated is recommended. Therapy with micafungin should be initiated after careful consideration of risks and benefits, particularly in patients with severe hepatic impairment or chronic hepatic diseases known to represent pre-neoplastic conditions (such as advanced hepatic fibrosis, cirrhosis, viral hepatitis, neonatal hepatic disease, congenital enzyme defects, and those receiving concurrent hepatotoxic and/or genotoxic medications).

Micafungin has been associated with significant impairment of hepatic function (increased ALT, AST or total bilirubin greater than 3 times the upper limit of normal) in healthy volunteers and patients. In some patients, more severe hepatic impairment, hepatitis and hepatic failure (including some fatal cases) have been reported. Paediatric patients under 1 year of age may be more susceptible to hepatic injury.

Micafungin therapy has been associated rarely with haemolysis, including acute intravascular haemolysis or haemolytic anaemia. Patients who develop clinical or laboratory evidence of haemolysis should be monitored closely for evidence of worsening of these conditions. The risk and benefits of continued micafungin therapy should be considered.

Animal studies have shown evidence of testicular toxicity. Micafungin may affect male fertility in humans.

Pregnancy and Lactation

Pregnancy

Micafungin is contraindicated during pregnancy.

The manufacturer does not recommend using micafungin during pregnancy. There are no data from the use of micafungin during human pregnancy. It should not be used unless clearly necessary. Micafungin caused reproductive toxicity and crossed the placental barrier in animal studies. It is unknown whether micafungin crosses the human placenta. The high molecular weight (about 1292 for the sodium salt), low lipid solubility, and very high protein binding should limit transfer to the embryo/foetus (Briggs 2015).

Lactation

Micafungin is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues micafungin or discontinues breastfeeding. It is not known if micafungin is excreted in human breast milk. Animal studies have shown that micafungin is excreted in breast milk. Briggs 2015, states that although the effect of exposure to micafungin in breast milk on a nursing infant is unknown, the risk appears to be low, if it exists at all. The high molecular weight (about 1292 for the sodium salt), low lipid solubility, and very high protein binding suggest that excretion into breast milk will be limited.

Side Effects

Abdominal pain
Abnormal liver function tests
Anaemia
Anaphylactic reaction
Anaphylactoid reaction
Anorexia
Anxiety
Blood urea increased
Bradycardia
Cholestasis
Confusion
Constipation
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dyspnoea
Eosinophilia
Erythema
Erythema multiforme
Flushing
Gamma glutamyl transferase (GGT) increased
Haemolysis
Haemolytic anaemia
Headache
Hepatic failure
Hepatitis
Hepatocellular damage
Hepatomegaly
Hyperbilirubinaemia
Hyperhidrosis
Hyperkalaemia
Hypersensitivity reactions
Hypertension
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Inflammation (injection site)
Insomnia
Intravascular coagulation (disseminated)
Jaundice
Leucopenia
Local pain (injection site)
Nausea
Neutropenia
Palpitations
Pancytopenia
Peripheral oedema
Phlebitis
Pruritus
Pyrexia
Rash
Renal failure
Renal impairment
Rigors
Serum bilirubin increased
Serum creatinine increased
Shock
Somnolence
Stevens-Johnson syndrome
Tachycardia
Thrombocytopenia
Thrombosis (injection site)
Toxic epidermal necrolysis
Toxic skin reaction
Tremor
Urticaria
Vomiting

Presentation

Infusions of micafungin (as sodium).

Drugs List

Therapeutic Indications

Uses

Candidal infection of the oesophagus: treatment
Prophylaxis of candida infection in haematopoietic stem cell transplant pts
Prophylaxis of candidiasis in pts expected to have neutropenia for 10+ days
Systemic candidiasis

Adults, elderly and adolescents aged 16 years or over

Treatment of invasive candidiasis.

Treatment of oesophageal candidiasis where intravenous therapy is appropriate.

Prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation.

Prophylaxis of Candida infection in patients expected to have neutropenia (absolute neutrophil count under 500 cells/microlitre) for 10 or more days.

Children aged under 16 years of age (including neonates)

Treatment of invasive candidiasis.

Prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation.

Prophylaxis of Candida infection in patients expected to have neutropenia (absolute neutrophil count under 500 cells/microlitre) for 10 or more days.

Micafungin should only be used where other antifungals are not appropriate. The decision to use micafungin should take into account the risk of liver tumour development.

Dosage

Treatment with micafungin should be initiated by a physician with experience in managing fungal infections.

Before therapy is started, specimens for fungal culture and other relevant laboratory tests (including histopathology) should be obtained in order to isolate and identify causative organisms. Therapy may begin before the results of these studies are known. However, antifungal therapy should be adjusted appropriately when results of these studies are obtained.

Adults

Children

Neonates

Administration

For intravenous infusion after reconstitution and dilution.

The infusion should be administered over one hour. More rapid infusions increase the risk of histamine mediated reactions.

Contraindications

Breastfeeding
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Children under 2 years
Chronic hepatic disorder
Extensive hepatic fibrosis
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hepatitis
Hereditary fructose intolerance
Lactose intolerance
Renal impairment

Advise patient ability to drive or operate machinery may be impaired
Consult national/regional policy on the use of anti-infectives
Treatment to be initiated and supervised by a specialist
Some formulations contain lactose
Some formulations contain sucrose
Monitor hepatic function
Monitor patient closely for haemolysis
Monitor renal function
Advise patients to report any unusual rash to the prescriber
May cause anaphylactic / anaphylactoid reactions
May induce or enhance hepatic tumour development
Discontinue if anaphylactoid reaction occurs
Discontinue if significant/persistent hepatic function abnormalities occur
Discontinue treatment if progressive skin rash occurs
Not licensed for all indications in all age groups
Male: May cause infertility

In studies with rats, the development of foci of altered hepatocytes and hepatocellular tumours were observed after a treatment period of 3 months or longer. The assumed threshold for tumour development in rats is approximately in the range of clinical exposure. The risk of these effects in humans cannot be excluded. Hepatic function should be carefully monitored during micafungin therapy. To reduce the risk of adaptive regeneration and potential hepatic tumour formation, the discontinuation of micafungin when ALT/AST levels are significantly and persistently elevated is recommended. Therapy with micafungin should be initiated after careful consideration of risks and benefits, particularly in patients with severe hepatic impairment or chronic hepatic diseases known to represent pre-neoplastic conditions (such as advanced hepatic fibrosis, cirrhosis, viral hepatitis, neonatal hepatic disease, congenital enzyme defects, and those receiving concurrent hepatotoxic and/or genotoxic medications).

Micafungin has been associated with significant impairment of hepatic function (increased ALT, AST or total bilirubin greater than 3 times the upper limit of normal) in healthy volunteers and patients. In some patients, more severe hepatic impairment, hepatitis and hepatic failure (including some fatal cases) have been reported. Paediatric patients under 1 year of age may be more susceptible to hepatic injury.

Micafungin therapy has been associated rarely with haemolysis, including acute intravascular haemolysis or haemolytic anaemia. Patients who develop clinical or laboratory evidence of haemolysis should be monitored closely for evidence of worsening of these conditions. The risk and benefits of continued micafungin therapy should be considered.

Animal studies have shown evidence of testicular toxicity. Micafungin may affect male fertility in humans.

Pregnancy and Lactation

Pregnancy

Micafungin is contraindicated during pregnancy.

The manufacturer does not recommend using micafungin during pregnancy. There are no data from the use of micafungin during human pregnancy. It should not be used unless clearly necessary. Micafungin caused reproductive toxicity and crossed the placental barrier in animal studies. It is unknown whether micafungin crosses the human placenta. The high molecular weight (about 1292 for the sodium salt), low lipid solubility, and very high protein binding should limit transfer to the embryo/foetus (Briggs 2015).

Lactation

Micafungin is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues micafungin or discontinues breastfeeding. It is not known if micafungin is excreted in human breast milk. Animal studies have shown that micafungin is excreted in breast milk. Briggs 2015, states that although the effect of exposure to micafungin in breast milk on a nursing infant is unknown, the risk appears to be low, if it exists at all. The high molecular weight (about 1292 for the sodium salt), low lipid solubility, and very high protein binding suggest that excretion into breast milk will be limited.

Side Effects

Abdominal pain
Abnormal liver function tests
Anaemia
Anaphylactic reaction
Anaphylactoid reaction
Anorexia
Anxiety
Blood urea increased
Bradycardia
Cholestasis
Confusion
Constipation
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dyspnoea
Eosinophilia
Erythema
Erythema multiforme
Flushing
Gamma glutamyl transferase (GGT) increased
Haemolysis
Haemolytic anaemia
Headache
Hepatic failure
Hepatitis
Hepatocellular damage
Hepatomegaly
Hyperbilirubinaemia
Hyperhidrosis
Hyperkalaemia
Hypersensitivity reactions
Hypertension
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Inflammation (injection site)
Insomnia
Intravascular coagulation (disseminated)
Jaundice
Leucopenia
Local pain (injection site)
Nausea
Neutropenia
Palpitations
Pancytopenia
Peripheral oedema
Phlebitis
Pruritus
Pyrexia
Rash
Renal failure
Renal impairment
Rigors
Serum bilirubin increased
Serum creatinine increased
Shock
Somnolence
Stevens-Johnson syndrome
Tachycardia
Thrombocytopenia
Thrombosis (injection site)
Toxic epidermal necrolysis
Toxic skin reaction
Tremor
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: November 2020

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Micafungin Teva 50mg and 100mg powder for concentrate for solution for infusion. Teva UK Ltd. Revised August 2020.

Summary of Product Characteristics: Micafungin Teva 50mg and 100mg powder for concentrate for solution for infusion. Wockhardt UK Ltd. Revised August 2020.

Summary of Product Characteristics: Mycamine 50mg and 100mg powder for solution for infusion. Astellas Pharma Ltd. Revised January 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 April 2021