AMPHOTERICIN B (conventional)

Antifungal activity

Should be used primarily for treatment of patients with potentially life-threatening fungal infections; it should not be used to treat noninvasive forms of fungal disease, in patients with normal neutrophil counts
Effective against many species of fungi: Histoplasma capsulatum, Coccidioides immitis, Candida sp., Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans , Sporothrix schenckii, Mucor sp.,  Aspergillus fumigatus

Pregnancy Risk Factor

Class B

Contraindication/Precaution

Should be used primarily for treatment of patients with potentially life-threatening fungal infections; it should not be used to treat noninvasive forms of fungal disease, in patients with normal neutrophil counts
Hypersensitivity to amphotericin , or any component
Anaphylaxis has been reported; facilities for cardiopulmonary resuscitation should be available
Should not be use while nursing
Use caution if impaired renal function
Safety and effectiveness in pediatric patients have not been established through adequate and well-controlled studies.
Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded. Overdoses can result in cardio-respiratory arrest
Topical preparations may stain clothing

Mechanism of Action

Fungistatic or fungicidal depending on the concentration in body fluids and the susceptibility of the fungus. 
Acts by binding to sterols in the cell membrane of susceptible fungi with a resultant change in membrane permeability allowing leakage of intercellular components. 

Pharmacodynamics

Metabolism: N/A
Half-life: biphasic, changes with renal function:
initial: ~24 hours
terminal: 15 days
Elimination: excreted in urine

Dosage

Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded. Overdoses can result in cardio-respiratory arrest

IV Tx:

Children: (max 1.5 mg/kg/day)

Safety and effectiveness in pediatric patients have not been established through adequate and well-controlled studies.

Pediatric patients with systemic fungal infections have been successfully treated without reports of unusual side effects.

Tx should be limited to the smallest dose compatible with an effective therapeutic regimen.

Test dose (not required): 
0.1 mg/kg/dose IV (max 1 mg/dose) infuse over 30-60 minutes

Maintenance dose: 
0.25-1 mg/kg IV qd infuse over 2-6 hours then once therapy has been established:
1-1.5 mg/kg q every other day  (cumulative dose: 1.5-2 g over 6-10 week)

Adults: (max 1.5 mg/kg/day):

Test dose (not required): 
1 mg IV  infuse over 30-60 minutes

Maintenance dose: 
0.25-0.3 mg/kg IV qd infuse over 4-6 hours then increase by 5-10 mg/kg/day 
once therapy has been established: 1-1.5 mg/kg q every other day (cumulative dose of 1-4 g over 4-12 weeks)

intra-thecal (IT) TX:

Children: (max 1.5 mg/kg/day)

Safety and effectiveness in pediatric patients have not been established through adequate and well-controlled studies.

Pediatric patients with systemic fungal infections have been successfully treated without reports of unusual side effects.

Tx should be limited to the smallest dose compatible with an effective therapeutic regimen.

Initial Tx:
25-100 mcg IT q48-72h then 
increase to 500 mcg IT q48-78h as tolerated

Adults: (max 1.5 mg/kg/day):

Initial Tx:
25-300 mcg IT q48-72h then 
increase to 500-1000 mcg IT q48-78h as tolerated for a max total Tx dose of 15 mg

oral Tx:

100 mg PO qid

topical Tx:

 Apply  2-4 times/day for 1-4 weeks

bladder irrigation: 

Irrigate with 50 mcg/ml solution periodically or continuously for 5-10 days or until cultures are clear

Dose VS renal function

Cr. clearance (ml/min):
<10: give q48h 10-50: give q24h 50-80: give q24h >80: give q24h

Dialysis
Hemo: none
CAPD: give q24-48h