Drugs List

Therapeutic Indications

Uses

Candidiasis - severe systemic
Cryptococcosis in AIDS patients
Fungal infection - systemic
Fungal infection after failed previous systemic therapy
Systemic fungal infection where conventional amphotericin contraindicated
Treatment of aspergillosis when other treatment unsuitable/ineffective
Treatment of cryptococcosis when other treatment unsuitable/ineffective

Administration

For intravenous infusion after dilution

Amphotericin should be administered by intravenous infusion at a rate of 2.5mg/kg/hour.

An in-line filter of mean pore diameter of no less than 15 microns may be used.

Contraindications

Neonates under 1 month
Long QT syndrome
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Breastfeeding
Electrolyte imbalance
Hepatic impairment
History of torsade de pointes
Pregnancy
Renal impairment

Correct electrolyte disorders before treatment
Sodium content of formulation may be significant
Avoid within 14 days of discontinuing sodium stibogluconate
Consult national/regional policy on the use of anti-infectives
Different preparations of intravenous amphotericin are not interchangeable
Do not add saline or electrolytes or other drugs to solution
Initial test dose should be given
Must be diluted before use
Resuscitation facilities must be immediately available
Consider monitoring ECG in patients at risk of QT prolongation
Monitor renal function in patients with renal impairment
Monitor serum electrolytes
Monitor serum magnesium regularly
Monitor serum potassium regularly

Pre-medication (e.g. paracetamol) should be considered to prevent infusion related adverse reactions.

Amphotericin lipid complex infusions should not be used for treating common or superficial fungal infections that are only detectable through positive skin or serologic tests.

Amphotericin is a potentially nephrotoxic drug, and thus renal function should be monitored before initiating treatment in patients with pre-existing renal disease or who have already experienced renal failure. This should occur at least once weekly during therapy.

Elderly patients show similar adverse reactions to amphotericin as adults under 65 years of age. However increased serum creatinine and dyspnoea were reported with a greater frequency for this age group.

Pregnancy and Lactation

Pregnancy

Use amphotericin lipid complex with caution during pregnancy.

A few case reports have indicated that conventional amphotericin B has been used successfully to treat systemic fungal infections in pregnant women with no obvious effects on the foetus. However, the safety of lipid formulations of amphotericin in pregnant women has not been established. Consequently, this infusion should only be administered to pregnant women when the likely benefit exceeds the risk to the mother and foetus.

Schaefer (2015) indicates that lipid formulations of amphotericin are preferred over conventional amphotericin. If administering lipid amphotericin during the first trimester, consider offering a detailed ultrasound to determine normal development of the foetus.

Amphotericin B crosses the placenta and cord blood concentrations are similar to those measured in the mother. Amphotericin B can be used in pregnancy if the mother will clearly benefit from its administration (Briggs, 2015)

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use amphotericin lipid complex with caution during breastfeeding.

Amphotericin B is permitted during breastfeeding. Although there are few reports on the use of amphotericin B during breastfeeding, due to the high protein binding, high molecular weight and poor oral absorption, one would expect infant uptake to be minimal (Schaefer, 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Anaphylactic reaction
Arrhythmias
Asthma
Blood urea increased
Bronchospasm
Cardiac arrest
Chills
Convulsions
Dyspnoea
Electrolyte disturbances
Encephalopathy
Exfoliative dermatitis
Headache
Hyperbilirubinaemia
Hyperkalaemia
Hypertension
Hypokalaemia
Hypomagnesaemia
Hyposthenuria
Hypotension
Increase in alkaline phosphatase
Injection site reactions
Myalgia
Nausea
Neuropathy
Pruritus
Pyrexia
Rash
Renal failure
Renal impairment
Renal tubular acidosis
Respiratory failure
Serum creatinine increased
Shock
Tachycardia
Thrombocytopenia
Tremor
Vomiting

Presentation

Concentrate for suspension for infusion containing amphotericin B lipid complex

Drugs List

Therapeutic Indications

Uses

Candidiasis - severe systemic
Cryptococcosis in AIDS patients
Fungal infection - systemic
Fungal infection after failed previous systemic therapy
Systemic fungal infection where conventional amphotericin contraindicated
Treatment of aspergillosis when other treatment unsuitable/ineffective
Treatment of cryptococcosis when other treatment unsuitable/ineffective

Dosage

Adults

Children

Administration

For intravenous infusion after dilution

Amphotericin should be administered by intravenous infusion at a rate of 2.5mg/kg/hour.

An in-line filter of mean pore diameter of no less than 15 microns may be used.

Contraindications

Neonates under 1 month
Long QT syndrome
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Breastfeeding
Electrolyte imbalance
Hepatic impairment
History of torsade de pointes
Pregnancy
Renal impairment

Correct electrolyte disorders before treatment
Sodium content of formulation may be significant
Avoid within 14 days of discontinuing sodium stibogluconate
Consult national/regional policy on the use of anti-infectives
Different preparations of intravenous amphotericin are not interchangeable
Do not add saline or electrolytes or other drugs to solution
Initial test dose should be given
Must be diluted before use
Resuscitation facilities must be immediately available
Consider monitoring ECG in patients at risk of QT prolongation
Monitor renal function in patients with renal impairment
Monitor serum electrolytes
Monitor serum magnesium regularly
Monitor serum potassium regularly

Pre-medication (e.g. paracetamol) should be considered to prevent infusion related adverse reactions.

Amphotericin lipid complex infusions should not be used for treating common or superficial fungal infections that are only detectable through positive skin or serologic tests.

Amphotericin is a potentially nephrotoxic drug, and thus renal function should be monitored before initiating treatment in patients with pre-existing renal disease or who have already experienced renal failure. This should occur at least once weekly during therapy.

Elderly patients show similar adverse reactions to amphotericin as adults under 65 years of age. However increased serum creatinine and dyspnoea were reported with a greater frequency for this age group.

Pregnancy and Lactation

Pregnancy

Use amphotericin lipid complex with caution during pregnancy.

A few case reports have indicated that conventional amphotericin B has been used successfully to treat systemic fungal infections in pregnant women with no obvious effects on the foetus. However, the safety of lipid formulations of amphotericin in pregnant women has not been established. Consequently, this infusion should only be administered to pregnant women when the likely benefit exceeds the risk to the mother and foetus.

Schaefer (2015) indicates that lipid formulations of amphotericin are preferred over conventional amphotericin. If administering lipid amphotericin during the first trimester, consider offering a detailed ultrasound to determine normal development of the foetus.

Amphotericin B crosses the placenta and cord blood concentrations are similar to those measured in the mother. Amphotericin B can be used in pregnancy if the mother will clearly benefit from its administration (Briggs, 2015)

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use amphotericin lipid complex with caution during breastfeeding.

Amphotericin B is permitted during breastfeeding. Although there are few reports on the use of amphotericin B during breastfeeding, due to the high protein binding, high molecular weight and poor oral absorption, one would expect infant uptake to be minimal (Schaefer, 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Anaphylactic reaction
Arrhythmias
Asthma
Blood urea increased
Bronchospasm
Cardiac arrest
Chills
Convulsions
Dyspnoea
Electrolyte disturbances
Encephalopathy
Exfoliative dermatitis
Headache
Hyperbilirubinaemia
Hyperkalaemia
Hypertension
Hypokalaemia
Hypomagnesaemia
Hyposthenuria
Hypotension
Increase in alkaline phosphatase
Injection site reactions
Myalgia
Nausea
Neuropathy
Pruritus
Pyrexia
Rash
Renal failure
Renal impairment
Renal tubular acidosis
Respiratory failure
Serum creatinine increased
Shock
Tachycardia
Thrombocytopenia
Tremor
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: June 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Amphotericin B Lipid Complex_Abelcet 5mg/mL Concentrate for Suspension for Infusion. Teva Pharma B.V. Revised January 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 9 June 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Amphotericin B. Last revised: 11 April 2017
Last accessed: 08 May 2017