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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Children
Neonates
Additional Dosage Information

Initially 250micrograms/kg daily, increasing gradually to 1mg/kg daily depending on individual response and tolerance.

Within the range of 250micrograms/kg to 1mg/kg the daily dose should be maintained at the highest level which is not accompanied by unacceptable toxicity.

If medication is interrupted for more than seven days, therapy should be resumed starting at the lowest dosage level (i.e. 250micrograms/kg, and increased gradually).

Severe infection:

The daily dose may be gradually increased up to a maximum of 1.5mg/kg.
As amphotericin is excreted slowly, the higher doses may be given on alternate days.
Several months of therapy are usually necessary. Shorter durations of therapy may produce inadequate response and relapse.
A total daily dose of 1.5mg/kg must NOT be exceeded.

Test dose

Severe infusion-related reactions can occur during administration, therefore it is advisable to give a test dose before a new course of treatment.
For this purpose, give a small amount of the infusion (e.g. 1mg in adults or 100micrograms/kg (up to a maximum 1mg) in children) over 20 to 30 minutes. Stop the infusion and observe the patient for the next 30 minutes.
If there have been no severe allergic or anaphylactic reactions, the infusion can be continued.
It must be noted that the patient's response to the test dose may not be indicative of subsequent severe side effects.

For patients who experience an acute and fast development of the fungal infection, and have good lung function as well as having good tolerance to the test dose with no serious side effects, administer 0.3mg/kg amphotericin B intravenously within the period of 2 to 6 hours. If patients experience serious side effects to the test dose or they suffer cardiopulmonary impairment, the suggested dose would be of 5mg to 10mg.

The dose can be increased by 5mg to 10mg daily to a maximum of 0.5mg/kg to 1mg/kg daily.

Other routes used

(In adult patients)
The use of amphotericin infusion by other routes has been documented:

Bladder irrigation/instillation (e.g. candiduria)

Continuous irrigation with 50mg amphotericin in 1 litre of sterile water daily until urinary cultures are negative.
Intermittent use of volumes of 100ml to 400ml (concentrations of 37.5micrograms/ml to 200micrograms/ml) have also been used.
The urine should be alkalinised (with potassium citrate) and antifungal ointment applied to the perineal area.

Lung inhalation (e.g. pulmonary aspergillosis)

8mg to 40mg amphotericin, nebulised in sterile water or glucose 5%, administered daily in divided doses.
Concurrent eradication of oral and intestinal yeast reservoirs is recommended.

Intrathecal (e.g. coccidioidal meningitis)

The intrathecal dosage of amphotericin normally ranges between 100micrograms and 1.5mg per dose, administered at intervals ranging from daily to weekly, beginning at a low dosage and increasing the dosage until the appearance of patient intolerance.
Amphotericin is irritating when injected into the cerebrospinal fluid.

Other

Solutions containing amphotericin have also been administered by local instillation for the treatment of fungal infections of the ear, eye, peritoneum, lung cavities and joint spaces.

Precautions and Warnings

Family history of long QT syndrome
Prior total body irradiation
Breastfeeding
Electrolyte imbalance
History of torsade de pointes
Pregnancy
Renal impairment

Correct electrolyte disorders before treatment
Avoid within 14 days of discontinuing sodium stibogluconate
May be used for hypersensitive patients only in life threatening situations
Treatment to be initiated by specialist
Different preparations of intravenous amphotericin are not interchangeable
Initial test dose should be given
Consider monitoring ECG in patients at risk of QT prolongation
Monitor full blood count regularly
Monitor hepatic function regularly
Monitor renal function regularly
Monitor serum electrolytes
Monitor serum magnesium regularly
Monitor serum potassium regularly
Discontinue if liver function tests become abnormal
Reduce dose and/or interrupt therapy if renal impairment worsens

It is essential to verify the product name and the dosage before administration to avoid overdose.

There is a risk of confusion between non-lipid formulations and lipid formulations of injectable amphotericin.

Care should be taken in the selection and administration of intravenous amphotericin preparations, especially with regard to dose calculations.

Severe infusion-related reactions, can occur during administration of amphotericin containing products.

Serum creatinine levels exceeding 260 micromole/litre, require product discontinuation or dosage reduction until renal function improves

While some patients may tolerate full intravenous doses of amphotericin without difficulty, most will exhibit some intolerance particularly during the initiation of therapy.

In patients experiencing adverse reactions these may be made less severe by giving aspirin, other antipyretics, antihistamines or anti-emetics.
Pethidine has been used in some patients to decrease the duration or intensity of shaking, chills and fever following amphotericin therapy.
Febrile reactions may be decreased by the intravenous administration of small doses of adrenal corticosteroids, e.g. hydrocortisone. This may be administered just prior to or during amphotericin infusion. The dosage and duration of such corticosteroid therapy should be kept to a minimum.

Amphotericin may be helpful in the treatment of American mucocutaneous leishmaniasis but is not the drug of choice for primary therapy.

Amphotericin should not be used to treat the common forms of fungal infection which show only positive skin or serological tests.

Pregnancy and Lactation

Pregnancy

Use amphotericin with caution in pregnancy.
The safety of using amphotericin in pregnant women has not been established. Manufacturer advises that amphotericin should be used during pregnancy only if the possible benefits to be derived outweigh the potential risks involved.

Systemic fungal infections have been successfully treated in pregnant women with conventional amphotericin without obvious effects on the foetus, but the number of cases reported has been small.
Amphotericin crosses the placenta and exposure to the foetus and neonate may be prolonged by its retention in the placenta and other tissue.

Schaefer (2007) advises that parenteral use during pregnancy should be restricted to dangerous disseminated mycoses.

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 with caution in breastfeeding.
It is not known whether amphotericin is excreted in human milk. As excretion of amphotericin in human milk is possible, and considering its potential toxicity, it should be used in nursing mothers only if the possible benefits to be derived outweigh the potential risks involved. In addition , it is prudent to advise a nursing mother to discontinue nursing.

Amphotericin is highly protein bound with a large molecular weight and virtually unabsorbed orally (less than 9%) and is unlikely to be clinically significant to a breastfeeding infant.

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

Presentation

Powder for concentrate for solution for infusion containing amphotericin

Drugs List

amphotericin 50mg powder for concentrate for solution for infusion

FUNGIZONE 50mg powder for concentrate for solution for infusion

Therapeutic Indications

Uses

Aspergillosis: treatment
Coccidioidomycosis: treatment
Cryptococcosis - treatment
Disseminated candidosis: treatment
Histoplasmosis
Mucormycosis: treatment
North American blastomycosis: treatment
Serious fungal infections

Dosage

Adults

Initially 250micrograms/kg daily, increasing gradually to 1mg/kg daily depending on individual response and tolerance.

Within the range of 250micrograms/kg to 1mg/kg the daily dose should be maintained at the highest level which is not accompanied by unacceptable toxicity.

If medication is interrupted for more than seven days, therapy should be resumed starting at the lowest dosage level (i.e. 250micrograms/kg, and increased gradually).

Severe infection:
The daily dose may be gradually increased up to a maximum of 1.5mg/kg.
As amphotericin is excreted slowly, the higher doses may be given on alternate days.
Several months of therapy are usually necessary. Shorter durations of therapy may produce inadequate response and relapse.
A total daily dose of 1.5mg/kg must NOT be exceeded.

Children

(See Dosage; Adult)

Neonates

Systemic fungal infections (unlicensed)
1mg/kg once daily. Increase if necessary to 1.5mg/kg daily.
After seven days, may be reduced to 1mg/kg to 1.5mg/kg on alternate days.

Additional Dosage Information

Test dose
Severe infusion-related reactions can occur during administration, therefore it is advisable to give a test dose before a new course of treatment.
For this purpose, give a small amount of the infusion (e.g. 1mg in adults or 100micrograms/kg (up to a maximum 1mg) in children) over 20 to 30 minutes. Stop the infusion and observe the patient for the next 30 minutes.
If there have been no severe allergic or anaphylactic reactions, the infusion can be continued.
It must be noted that the patient's response to the test dose may not be indicative of subsequent severe side effects.

The dose can be increased by 5mg to 10mg daily to a maximum of 0.5mg/kg to 1mg/kg daily.

Other routes used
(In adult patients)
The use of amphotericin infusion by other routes has been documented:

Bladder irrigation/instillation (e.g. candiduria)
Continuous irrigation with 50mg amphotericin in 1 litre of sterile water daily until urinary cultures are negative.
Intermittent use of volumes of 100ml to 400ml (concentrations of 37.5micrograms/ml to 200micrograms/ml) have also been used.
The urine should be alkalinised (with potassium citrate) and antifungal ointment applied to the perineal area.

Lung inhalation (e.g. pulmonary aspergillosis)
8mg to 40mg amphotericin, nebulised in sterile water or glucose 5%, administered daily in divided doses.
Concurrent eradication of oral and intestinal yeast reservoirs is recommended.

Intrathecal (e.g. coccidioidal meningitis)
The intrathecal dosage of amphotericin normally ranges between 100micrograms and 1.5mg per dose, administered at intervals ranging from daily to weekly, beginning at a low dosage and increasing the dosage until the appearance of patient intolerance.
Amphotericin is irritating when injected into the cerebrospinal fluid.
Other
Solutions containing amphotericin have also been administered by local instillation for the treatment of fungal infections of the ear, eye, peritoneum, lung cavities and joint spaces.

Administration

For intravenous infusion. Recommended concentration for intravenous infusion is 10 mg/100ml.

Bladder irrigation/instillation.
Inhalation.
Intrathecal injection.
Local instillation.

Contraindications

Long QT syndrome
Torsade de pointes