Doses - AMPHOTERICIN B
Note: Some clinicians have recommended administering a 1 mg test dose (less in small dogs orcats) IV over anywhere from 20 minutes to 4 hours and monitoring pulse, respiration rates, temperature, and if possible, blood pressure. If a febrile reaction occurs some clinicians recommendadding a glucocorticoid to the IV infusion solution or using an antipyretic prior to treating, but thesepractices are controversial.
A recently published study (Rubin et al. 1989) demonstrated less renal impairment and systemicadverse effects in dogs who received amphotericin B IV slowly over 5 hours in 1 L of D5W than indogs who received the drug IV in 25 ml of D5W over 3 minutes.Dogs:
For treatment of susceptible systemic fungal infections:
a) Two regimens can be used; after diluting vial (as outlined below in preparation of solution section), either:
1) Rapid-Infusion Technique:
Dilute quantity of stock solution to equal 0.25 mg/kg in 30 ml of 5% dextrose. Usingbutterfly catheter, flush with 10 ml of D5W. Infuse amphotericin B solution IV over 5minutes. Flush catheter with 10 ml of D5W and remove catheter. Repeat above stepsusing 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given.
2) Slow IV Infusion Technique:
Dilute quantity of stock solution to equal 0.25 mg/kg in 250 - 500 ml of D5W. Placeindwelling catheter in peripheral vein and give total volume over 4-6 hours. Flushcatheter with 10 ml of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3times a week until 9-12 mg/kg accumulated dosage is given. (Noxon 1989)
b) In dehydrated, sodium-depleted animals, must rehydrate before administration. Dosageis 0.5 mg/kg diluted in D5W. In dogs with normal renal function, may dilute in 60-120ml of D5W and give by slow IV over 15 minutes. In dogs with compromised renalfunction, dilute in 500 ml or 1 l of D5W and give over slowly IV over 3-6 hours.
Readminister every other day if BUN remains below 50 mg/dl. If BUN exceeds 50mg/dl, discontinue until BUN decreases to at least 35 mg/dl. Cumulative dose of 8-10mg/kg is required to cure blastomycosis or histoplasmosis. Coccidioidomycosis, aspergillosis and other fungal diseases require a greater cululative dosage. (Legendre1995)
For blastomycosis (see general dosage guidelines above) :
a) Amphotericin B 0.5 mg/kg 3 times weekly until a total dose of 6 mg/kg is given, with ketoconazole at 10 - 20 mg/kg (30 mg/kg for CNS, bone or eye involvement) divided for 3-6 months. (Foil 1986)
b) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 20 mg/day POonce daily or divided bid; 40 mg/kg divided bid for ocular or CNS involvement (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4 - 6 mg/kg start maintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided bid or ketoconazole at 2.5 - 5 mg/kg PO once daily. If CNS/ocular involvement use ketoconazole at 20 - 40 mg/kg PO divided bid. (Greene, O'Neal, and Barsanti 1984)
For cryptococcosis (see general dosage guidelines above):
a) Amphotericin B 0.15 - 0.4 mg/kg IV 3 times a week with flucytosine 150 - 175 mg/kg
PO divided tid-qid. When a total dose of amphotericin B reaches 4 - 6 mg/kg start maintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month with flucytosine at dosage above or with ketoconazole at 10 mg/kg PO once daily or divided bid. (Greene, O'Neal, and Barsanti 1984)
For histoplasmosis (see general dosage guidelines above):
a) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 10 - 20 mg/day
PO once daily or divided bid (for at least 2-3 months or until remission then startmaintenance). When a total dose of amphotericin B reaches 2 - 4 mg/kg startmaintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or useketoconazole at 10 mg/kg PO either once daily, divided bid or at 2.5 - 5 mg/kg PO oncedaily. (Greene, O'Neal, and Barsanti 1984)
b) As an alternative to ketoconazole treatment: 0.5 mg/kg IV given over 6-8 hours. If doseis tolerated, increase to 1 mg/kg given on alternate day until total dose of 7.5-8.5 mg/kgcumulative dose is achieved. (Macy 1987)Cats:
For treatment of susceptible systemic fungal infections:
a) Rapid-Infusion Technique: After diluting vial (as outlined below in preparation ofsolution section), dilute quantity of stock solution to equal 0.25 mg/kg in 30 ml of 5%dextrose. Using butterfly catheter, flush with 10 ml of D5W. Infuse amphotericin Bsolution IV over 5 minutes. Flush catheter with 10 ml of D5W and remove catheter.
Repeat above steps using 0.25 mg/kg 3 times a week until 9-12 mg/kg accumulateddosage is given. (Noxon 1989)
For cryptococcosis (see general dosage guidelines above):
a) As an alternative therapy to ketoconazole: Amphotericin B: 0.25 mg/kg in 30 ml D5W IV over 15 minutes q48h with flucytosine: 200 mg/kg/day divided q6h PO. Continuetherapy for 3-4 weeks after clinical signs have resolved or until BUN > 50 mg/dl.(Legendre 1989)
b) Amphotericin B 0.15 - 0.4 mg/kg IV 3 times a week with flucytosine 125 - 250 mg/day
PO divided bid-qid. When a total dose of amphotericin B reaches 4 - 6 mg/kg startmaintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month withflucytosine at dosage above or with ketoconazole at 10 mg/kg PO once daily or dividedbid. (Greene, O'Neal, and Barsanti 1984)
For histoplasmosis (see general dosage guidelines above):
a) Amphotericin B: 0.25 mg/kg in 30 ml D5W IV over 15 minutes q48h with ketoconazole: 10 mg/kg q12h PO. Continue therapy for 4-8 weeks or until BUN > 50 mg/dl. If
BUN increases greater than 50 mg/dl, continue ketoconazole alone. Ketoconazole isused long-term (at least 6 months of duration. (Legendre 1989)
b) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day POonce daily or divided bid (for at least 2-3 months or until remission, then start maintenance). When a total dose of amphotericin B reaches 2 - 4 mg/kg start maintenancedosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or use ketoconazole at10 mg/kg PO either once daily, divided bid or at 2.5 - 5 mg/kg PO once daily. (Greene,
O'Neal, and Barsanti 1984)
For blastomycosis (see general dosage guidelines above):
a) Amphotericin B: 0.25 mg/kg in 30 ml D5W IV over 15 minutes q48h with ketoconazole: 10 mg/kg q12h PO (for at least 60 days). Continue amphotericin B therapy until acumulative dose of 4 mg/kg is given or until BUN > 50 mg/dl. If renal toxicity does notdevelop, may increase dose to 0.5 mg/kg of amphotericin B. (Legendre 1989)
b) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day POonce daily or divided bid (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4 - 6 mg/kg start maintenancedosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or use ketoconazole at10 mg/kg PO either once daily, divided bid or ketoconazole at 2.5 - 5 mg/kg PO oncedaily. If CNS/ocular involvement, use ketoconazole at 20 - 40 mg/kg PO divided bid.(Greene, O'Neal, and Barsanti 1984)Horses:
For treatment of susceptible systemic fungal infections:
a) 0.3 mg/kg in D5W IV (Robinson 1987)
b) For phycomycoses and pulmonary mycoses: After reconstitution (see below) transferappropriate amount of drug to 1L of D5W and administer using a 16 g needle IV at arate of 1 L/hr. Dosage schedule follows:
Day 1: 0.3 mg/kg IV
Day 2: 0.45 mg/kg IV
Day 3: 0.6 mg/kg IV; then every other day for 3 days per week (MWF or TTHSa) untilclinical signs of improvement or toxicity takes place. It toxicity occurs, a dose may beskipped, dose reduced or dosage interval lengthened. Administration may extend from10-80 days. (Brumbaugh 1987)
Llamas:
For treatment of susceptible systemic fungal infections:
a) A single case report. Llama received 1 mg test dose, then initially at 0.3 mg/kg IV over 4hours, followed by 3 L of LRS with 1.5 ml of B-Complex and 20 mEq of KCl added.
Subsequent doses were increased by 10 mg and given every 48 hours until reaching 1mg/kg q48h IV for 6 weeks. Animal tolerated therapy well, but treatment was ultimatelyunsuccessful (Coccidiodomycoses). (Fowler 1989)Birds:
For treatment of susceptible systemic fungal infections:
a) For raptors and psittacines with aspergillosis: 1.5 mg/kg IV tid for 3 days with flucytosine or follow with flucytosine.
May also use intratracheally at 1 mg/kg diluted in sterile water once to 3 times daily for3 days in conjunction with flucytosine or nebulized (1 mg/ml of saline) for 15 minutesbid.
Potentially nephrotoxic and may cause bone marrow suppression. (Clubb 1986)Reptiles:
For susceptible fungal respiratory infections:
a) For most species: 1 mg/kg diluted in saline and given intra tracheally once daily for 14-28 treatments (Gauvin 1993)
Monitoring Parameters - Also see Adverse effects section1) BUN and serum creatinine every other day while dosage is being increased, and at least weekly thereafter during therapy 2) Serum electrolytes (sodium, potassium and magnesium) weekly 3) Liver function tests weekly 4) CBC weekly 5) Urinalysis weekly 6) TPP at least weekly 7) Animal's weight
Client Information - Clients should be informed of the potential seriousness of toxic effects thatcan occur with amphotericin B therapy, as well as the costs associated with therapy.
Dosage Forms/Preparations/FDA Approval Status/Solution Preparation - Veterinary-Approved Products: None
Directions for reconstitution/administration: Using strict aseptic technique and a 20 gauge orlarger needle, rapidly inject 10 ml of sterile water for injection (without a bacteriostaticagent) directly into the lyophylized cake; immediately shake well until solution is clear. A5 mg/ml colloidal solution results. Further dilute (1:50) for administration to aconcentration of 0.1 mg/ml with 5% dextrose in water (pH >4.2). An in-line filter may beused during administration, but must have a pore diameter >1 micron.
Amphotericin B Suspension for Injection: 100 mg/20 ml (as lipid complex) in single use vialswith 5 micron filter needles: Abelcet® (Liposome Co.) (Rx)
Amphotericin B for Powder for Injection 50 mg/vial (as cholesteryl) in 20 ml vials with 52.8 mgsodium cholesteryl sulfate & 100 mg (as cholesteryl) in 50 ml vials with 52.8 mg sodiumcholesteryl sulfate; Amphotec® (Sequus Pharmaceuticals) (Rx)
Amphotericin B for Powder for Injection 50 mg/vial (as liposomal) in single use vials with 5micron filter needles:AmBisome® (Fujisawa) (Rx)
Amphotericin B is also available in a topical formulation.
A recently published study (Rubin et al. 1989) demonstrated less renal impairment and systemicadverse effects in dogs who received amphotericin B IV slowly over 5 hours in 1 L of D5W than indogs who received the drug IV in 25 ml of D5W over 3 minutes.
Dogs: 
For treatment of susceptible systemic fungal infections: a) Two regimens can be used; after diluting vial (as outlined below in preparation of solution section), either:
1) Rapid-Infusion Technique:
Dilute quantity of stock solution to equal 0.25 mg/kg in 30 ml of 5% dextrose. Usingbutterfly catheter, flush with 10 ml of D5W. Infuse amphotericin B solution IV over 5minutes. Flush catheter with 10 ml of D5W and remove catheter. Repeat above stepsusing 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given.
2) Slow IV Infusion Technique:
Dilute quantity of stock solution to equal 0.25 mg/kg in 250 - 500 ml of D5W. Placeindwelling catheter in peripheral vein and give total volume over 4-6 hours. Flushcatheter with 10 ml of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3times a week until 9-12 mg/kg accumulated dosage is given. (Noxon 1989)
b) In dehydrated, sodium-depleted animals, must rehydrate before administration. Dosageis 0.5 mg/kg diluted in D5W. In dogs with normal renal function, may dilute in 60-120ml of D5W and give by slow IV over 15 minutes. In dogs with compromised renalfunction, dilute in 500 ml or 1 l of D5W and give over slowly IV over 3-6 hours.
Readminister every other day if BUN remains below 50 mg/dl. If BUN exceeds 50mg/dl, discontinue until BUN decreases to at least 35 mg/dl. Cumulative dose of 8-10mg/kg is required to cure blastomycosis or histoplasmosis. Coccidioidomycosis, aspergillosis and other fungal diseases require a greater cululative dosage. (Legendre1995)
For blastomycosis (see general dosage guidelines above) :
a) Amphotericin B 0.5 mg/kg 3 times weekly until a total dose of 6 mg/kg is given, with ketoconazole at 10 - 20 mg/kg (30 mg/kg for CNS, bone or eye involvement) divided for 3-6 months. (Foil 1986)
b) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 20 mg/day POonce daily or divided bid; 40 mg/kg divided bid for ocular or CNS involvement (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4 - 6 mg/kg start maintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided bid or ketoconazole at 2.5 - 5 mg/kg PO once daily. If CNS/ocular involvement use ketoconazole at 20 - 40 mg/kg PO divided bid. (Greene, O'Neal, and Barsanti 1984)
For cryptococcosis (see general dosage guidelines above):
a) Amphotericin B 0.15 - 0.4 mg/kg IV 3 times a week with flucytosine 150 - 175 mg/kg
PO divided tid-qid. When a total dose of amphotericin B reaches 4 - 6 mg/kg start maintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month with flucytosine at dosage above or with ketoconazole at 10 mg/kg PO once daily or divided bid. (Greene, O'Neal, and Barsanti 1984)
For histoplasmosis (see general dosage guidelines above):
a) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 10 - 20 mg/day
PO once daily or divided bid (for at least 2-3 months or until remission then startmaintenance). When a total dose of amphotericin B reaches 2 - 4 mg/kg startmaintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or useketoconazole at 10 mg/kg PO either once daily, divided bid or at 2.5 - 5 mg/kg PO oncedaily. (Greene, O'Neal, and Barsanti 1984)
b) As an alternative to ketoconazole treatment: 0.5 mg/kg IV given over 6-8 hours. If doseis tolerated, increase to 1 mg/kg given on alternate day until total dose of 7.5-8.5 mg/kgcumulative dose is achieved. (Macy 1987)
Cats: 
For treatment of susceptible systemic fungal infections: a) Rapid-Infusion Technique: After diluting vial (as outlined below in preparation ofsolution section), dilute quantity of stock solution to equal 0.25 mg/kg in 30 ml of 5%dextrose. Using butterfly catheter, flush with 10 ml of D5W. Infuse amphotericin Bsolution IV over 5 minutes. Flush catheter with 10 ml of D5W and remove catheter.
Repeat above steps using 0.25 mg/kg 3 times a week until 9-12 mg/kg accumulateddosage is given. (Noxon 1989)
For cryptococcosis (see general dosage guidelines above):
a) As an alternative therapy to ketoconazole: Amphotericin B: 0.25 mg/kg in 30 ml D5W IV over 15 minutes q48h with flucytosine: 200 mg/kg/day divided q6h PO. Continuetherapy for 3-4 weeks after clinical signs have resolved or until BUN > 50 mg/dl.(Legendre 1989)
b) Amphotericin B 0.15 - 0.4 mg/kg IV 3 times a week with flucytosine 125 - 250 mg/day
PO divided bid-qid. When a total dose of amphotericin B reaches 4 - 6 mg/kg startmaintenance dosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month withflucytosine at dosage above or with ketoconazole at 10 mg/kg PO once daily or dividedbid. (Greene, O'Neal, and Barsanti 1984)
For histoplasmosis (see general dosage guidelines above):
a) Amphotericin B: 0.25 mg/kg in 30 ml D5W IV over 15 minutes q48h with ketoconazole: 10 mg/kg q12h PO. Continue therapy for 4-8 weeks or until BUN > 50 mg/dl. If
BUN increases greater than 50 mg/dl, continue ketoconazole alone. Ketoconazole isused long-term (at least 6 months of duration. (Legendre 1989)
b) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day POonce daily or divided bid (for at least 2-3 months or until remission, then start maintenance). When a total dose of amphotericin B reaches 2 - 4 mg/kg start maintenancedosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or use ketoconazole at10 mg/kg PO either once daily, divided bid or at 2.5 - 5 mg/kg PO once daily. (Greene,
O'Neal, and Barsanti 1984)
For blastomycosis (see general dosage guidelines above):
a) Amphotericin B: 0.25 mg/kg in 30 ml D5W IV over 15 minutes q48h with ketoconazole: 10 mg/kg q12h PO (for at least 60 days). Continue amphotericin B therapy until acumulative dose of 4 mg/kg is given or until BUN > 50 mg/dl. If renal toxicity does notdevelop, may increase dose to 0.5 mg/kg of amphotericin B. (Legendre 1989)
b) Amphotericin B 0.15 - 0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day POonce daily or divided bid (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4 - 6 mg/kg start maintenancedosage of amphotericin B at 0.15 - 0.25 mg/kg IV once a month or use ketoconazole at10 mg/kg PO either once daily, divided bid or ketoconazole at 2.5 - 5 mg/kg PO oncedaily. If CNS/ocular involvement, use ketoconazole at 20 - 40 mg/kg PO divided bid.(Greene, O'Neal, and Barsanti 1984)
Horses: 
For treatment of susceptible systemic fungal infections: a) 0.3 mg/kg in D5W IV (Robinson 1987)
b) For phycomycoses and pulmonary mycoses: After reconstitution (see below) transferappropriate amount of drug to 1L of D5W and administer using a 16 g needle IV at arate of 1 L/hr. Dosage schedule follows:
Day 1: 0.3 mg/kg IV
Day 2: 0.45 mg/kg IV
Day 3: 0.6 mg/kg IV; then every other day for 3 days per week (MWF or TTHSa) untilclinical signs of improvement or toxicity takes place. It toxicity occurs, a dose may beskipped, dose reduced or dosage interval lengthened. Administration may extend from10-80 days. (Brumbaugh 1987)
Llamas:
For treatment of susceptible systemic fungal infections:
a) A single case report. Llama received 1 mg test dose, then initially at 0.3 mg/kg IV over 4hours, followed by 3 L of LRS with 1.5 ml of B-Complex and 20 mEq of KCl added.
Subsequent doses were increased by 10 mg and given every 48 hours until reaching 1mg/kg q48h IV for 6 weeks. Animal tolerated therapy well, but treatment was ultimatelyunsuccessful (Coccidiodomycoses). (Fowler 1989)
Birds: 
For treatment of susceptible systemic fungal infections: a) For raptors and psittacines with aspergillosis: 1.5 mg/kg IV tid for 3 days with flucytosine or follow with flucytosine.
May also use intratracheally at 1 mg/kg diluted in sterile water once to 3 times daily for3 days in conjunction with flucytosine or nebulized (1 mg/ml of saline) for 15 minutesbid.
Potentially nephrotoxic and may cause bone marrow suppression. (Clubb 1986)
Reptiles: 
For susceptible fungal respiratory infections: a) For most species: 1 mg/kg diluted in saline and given intra tracheally once daily for 14-28 treatments (Gauvin 1993)
Monitoring Parameters - Also see Adverse effects section
Client Information - Clients should be informed of the potential seriousness of toxic effects thatcan occur with amphotericin B therapy, as well as the costs associated with therapy.
Dosage Forms/Preparations/FDA Approval Status/Solution Preparation - Veterinary-Approved Products: None
Human-Approved Products:
Amphotericin B for Powder for Injection 50 mg/vial (as deoxycholate); Fungizone® Intravenous(Bristol-Myers Squibb); (Rx); Amphotericin B® (Pharma-Tek); (Rx)Directions for reconstitution/administration: Using strict aseptic technique and a 20 gauge orlarger needle, rapidly inject 10 ml of sterile water for injection (without a bacteriostaticagent) directly into the lyophylized cake; immediately shake well until solution is clear. A5 mg/ml colloidal solution results. Further dilute (1:50) for administration to aconcentration of 0.1 mg/ml with 5% dextrose in water (pH >4.2). An in-line filter may beused during administration, but must have a pore diameter >1 micron.
Amphotericin B Suspension for Injection: 100 mg/20 ml (as lipid complex) in single use vialswith 5 micron filter needles: Abelcet® (Liposome Co.) (Rx)
Amphotericin B for Powder for Injection 50 mg/vial (as cholesteryl) in 20 ml vials with 52.8 mgsodium cholesteryl sulfate & 100 mg (as cholesteryl) in 50 ml vials with 52.8 mg sodiumcholesteryl sulfate; Amphotec® (Sequus Pharmaceuticals) (Rx)
Amphotericin B for Powder for Injection 50 mg/vial (as liposomal) in single use vials with 5micron filter needles:AmBisome® (Fujisawa) (Rx)
Amphotericin B is also available in a topical formulation.