Amphotericin B
Amphotericin B is a polyene antifungal used for serious systemic mycoses, especially when rapid or intensive treatment is needed. Veterinary experience includes disseminated blastomycosis, histoplasmosis and coccidioidomycosis. Its usefulness is balanced against infusion reactions and renal toxicity, which are strongly influenced by formulation and exposure.
Conventional deoxycholate, lipid-complex, colloidal-dispersion and liposomal products are distinct preparations. Lipid-associated delivery can alter distribution and reduce nephrotoxicity, but these products are not interchangeable milligram for milligram and do not remove the need for formulation-specific regimens.
Group
Polyene antifungal
Mechanism of Action
Amphotericin B binds preferentially to ergosterol in fungal cell membranes. Association with membrane sterols disrupts membrane organization and permeability, allowing loss of intracellular ions and other small constituents. The resulting loss of cellular homeostasis can produce fungal cell death.
The drug can also interact with mammalian membrane sterols and affect renal cells and renal blood flow. These host effects help explain nephrotoxicity and electrolyte disturbances despite preferential antifungal activity. Toxicity is therefore not simply a consequence of killing a large number of fungi.
Lipid-based formulations change how amphotericin is carried and delivered to tissues, reducing exposure of some vulnerable host structures while preserving antifungal activity. Differences in carrier structure and distribution explain why one product’s dose, infusion method or cumulative exposure cannot automatically be transferred to another.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Systemic mycosis – conventional formulation | 0.5 mg/kg | IV | Every 48 h | Slow infusion. Track a cumulative course amount of 4–8 mg/kg; a cumulative per-kg cap is not supported by this calculator. |
| Systemic mycosis – lipid formulation course — Initial | 0.5 mg/kg | IV | Once | First dose of a formulation-specific course; infuse over 60–120 minutes, then increase only if tolerated. Subsequent course: 1–3 mg/kg every other day or three times weekly, up to 9–12 treatments and cumulative 12–36 mg/kg. |
| Systemic mycosis – lipid formulation course — Maintenance | 1–3 mg/kg | IV | Every other day or three times weekly after tolerated initial treatment; infuse over 60–120 minutes. Course target 12–36 mg/kg cumulative, up to 9–12 treatments; transition to an oral azole may occur earlier. | |
| Systemic mycosis – Abelcet alternative — Initial | 0.5 mg/kg | IV | Once | Infuse first dose over 90–120 minutes. If tolerated, use 2–3 mg/kg on alternate days; cumulative goal 12–36 mg/kg. Dilute to 1 mg/mL in 5% dextrose, or further when needed. |
| Systemic mycosis – Abelcet alternative — Maintenance | 2–3 mg/kg | IV | Every 48 h | After tolerated initial dose, dilute in 5% dextrose to 1 mg/mL or lower. Cumulative target 12–36 mg/kg; transition to an oral azole may occur earlier. |
| Blastomycosis – Abelcet study course | 1 mg/kg | IV | Every 48 h | Lipid complex course with cumulative exposure 8–12 mg/kg; cumulative per-kg tracking is required. |
| Systemic mycosis – subcutaneous course | 0.5–0.8 mg/kg | SC | Two or three times weekly. Dilute in 500 mL of 0.45% saline/2.5% dextrose for dogs under 20 kg or 1000 mL for dogs over 20 kg; final concentration must not exceed 20 mg/L. Exactly 20 kg is not assigned a fluid volume. Sterile abscesses may occur. | |
| Leishmaniasis | 0.5 mg/kg | IV | Every 48 h | Up to 28 days; Slow infusion; resistance concerns discourage this use and cumulative exposure requires tracking. |
| Slow conventional infusion | 0.25–0.5 mg/kg | IV | First 0.25 mg/kg in 250–500 mL D5W over 4–6 hours, then 0.5 mg/kg three times weekly to a cumulative 9–12 mg/kg; flush catheter with 10 mL D5W. | |
| Rapid conventional historical infusion | 0.25–0.5 mg/kg | IV | First 0.25 mg/kg in 30 mL D5W over 5 minutes, then 0.5 mg/kg three times weekly to cumulative 9–12 mg/kg; flush before and after with 10 mL D5W. Slow infusion has shown less renal injury than rapid administration. | |
| Conventional alternate-day course | 0.5 mg/kg | IV | Every 48 h | Normal renal function: 60–120 mL D5W over 15 minutes. Compromised function: 500–1000 mL over 3–6 hours. Rehydrate first. Stop if BUN exceeds 50 mg/dL and resume only after it falls to 35 mg/dL or less. Blastomycosis/histoplasmosis target cumulative 8–10 mg/kg. |
| Lipid-based systemic mycosis alternative | 1–2.5 mg/kg | IV | Every 48 h | Up to 28 days; After 0.5 mg/kg test dose, use alternate days or Monday/Wednesday/Friday. Susceptible yeasts/dimorphic fungi: 1 mg/kg to cumulative 12 mg/kg. Resistant filamentous infections: 2–2.5 mg/kg to cumulative 24–30 mg/kg. |
| Abelcet systemic mycosis – three-times-weekly course | 2–3 mg/kg | IV | Three times weekly for 9–12 treatments or cumulative 24–27 mg/kg; dilute to 1 mg/mL in D5W and infuse over 1–2 hours. | |
| Blastomycosis – conventional ketoconazole combination | 0.5 mg/kg | IV | Three times weekly until cumulative 6 mg/kg. Ketoconazole total daily amount 10–20 mg/kg, or 30 mg/kg for CNS/bone/eye involvement, divided through the day for 3–6 months; its division frequency is not specified. | |
| Blastomycosis – staged conventional combination | 0.15–0.5 mg/kg | IV | Three times weekly with an azole. At cumulative 4–6 mg/kg, change to 0.15–0.25 mg/kg IV monthly or an appropriate oral azole. Some accompanying ketoconazole amounts lack a /kg denominator, so they are not adopted as universal doses. | |
| Histoplasmosis – staged conventional combination | 0.15–0.5 mg/kg | IV | Three times weekly with an azole. At cumulative 2–4 mg/kg, change to 0.15–0.25 mg/kg IV monthly or an appropriate oral azole. Some accompanying ketoconazole amounts lack a /kg denominator, so they are not adopted as universal doses. | |
| Blastomycosis – severe disease lipid complex | 1–2 mg/kg | IV | Every 48 h | Abelcet every other day or three times weekly to cumulative 12–24 mg/kg. |
| Cryptococcosis – SC course | 0.5–0.8 mg/kg | SC | Two or three times weekly in 0.45% saline/2.5% dextrose, using 500 mL under 20 kg or 1000 mL over 20 kg; concentration must not exceed 20 mg/L. May combine with flucytosine or an azole. Risk of sterile abscesses. | |
| Histoplasmosis – escalating conventional alternative | 0.5–1 mg/kg | IV | Every 48 h | Initial 0.5 mg/kg over 6–8 hours; if tolerated increase to 1 mg/kg on alternate days until cumulative 7.5–8.5 mg/kg. |
| Leishmaniasis – short liposomal course | 3–3.3 mg/kg | IV | Three times weekly for 3–5 treatments; preserve true liposomal formulation. | |
| Leishmaniasis – AmBisome course | 3–3.3 mg/kg | IV | Every 72–96 h | After 0.5 mg/kg test dose, continue until cumulative 15 mg/kg. An unspecified lower-dose every-48-hour variant is not converted into a guessed amount. |
| Gastrointestinal pythiosis – postoperative lipid complex | 1–2 mg/kg | IV | Up to 28 days; Abelcet three times weekly after resection with 5–6 cm margins; stated cumulative amount lacks /kg in one passage. Do not infer a fixed-total cap. Alternative itraconazole 10 mg/kg PO daily for 4–6 months is described. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Systemic mycosis – conventional formulation | 0.25 mg/kg | IV | An example amount is listed, but no feline-specific interval is given; some clinicians start lower. Do not assume the canine schedule. | |
| Systemic mycosis – liposomal formulation | 1 mg/kg | IV | Three times weekly for up to 12 treatments; preserve formulation and course limits. | |
| Blastomycosis – staged conventional combination | 0.15–0.5 mg/kg | IV | Three times weekly with an azole. At cumulative 4–6 mg/kg, change to 0.15–0.25 mg/kg IV monthly or an appropriate oral azole. Some accompanying ketoconazole amounts lack a /kg denominator, so they are not adopted as universal doses. | |
| Histoplasmosis – staged conventional combination | 0.15–0.5 mg/kg | IV | Three times weekly with an azole. At cumulative 2–4 mg/kg, change to 0.15–0.25 mg/kg IV monthly or an appropriate oral azole. Some accompanying ketoconazole amounts lack a /kg denominator, so they are not adopted as universal doses. | |
| Cryptococcosis – SC course | 0.5–0.8 mg/kg | SC | Two or three times weekly in 0.45% saline/2.5% dextrose, using 400 mL; concentration must not exceed 20 mg/L. May combine with flucytosine or an azole. Risk of sterile abscesses. | |
| Conventional three-times-weekly course | 0.25 mg/kg | IV | First and subsequent doses 0.25 mg/kg in 30 mL D5W over 5 minutes, with 10 mL D5W catheter flushes; cumulative target 9–12 mg/kg. Rapid administration carries greater renal-risk concern. | |
| Cryptococcosis – conventional flucytosine course | 0.25 mg/kg | IV | Every 48 h | In 30 mL D5W over 15 minutes with flucytosine 200 mg/kg/day divided every 6 hours PO. Continue 3–4 weeks after resolution or until BUN exceeds 50 mg/dL. |
| Cryptococcosis – staged conventional combination | 0.15–0.4 mg/kg | IV | Three times weekly with flucytosine; at cumulative 4–6 mg/kg change to 0.15–0.25 mg/kg IV monthly. The paired fixed flucytosine amount is not a universal weight-based dose. | |
| Systemic mycosis – Abelcet course | 1 mg/kg | IV | Three times weekly for 12 treatments, diluted to 1 mg/mL in D5W over 1–2 hours. The stated cumulative total lacks /kg; track the administered per-kg course without inventing an amount-only cap. | |
| Histoplasmosis – conventional ketoconazole course | 0.25 mg/kg | IV | Every 48 h | Up to 56 days; 4–8 weeks, 30 mL D5W over 15 minutes; ketoconazole 10 mg/kg PO every 12 hours for at least 6 months. Stop amphotericin if BUN exceeds 50 mg/dL. |
| Blastomycosis – conventional ketoconazole course | 0.25–0.5 mg/kg | IV | Every 48 h | Start 0.25 mg/kg in 30 mL D5W over 15 minutes; may increase to 0.5 mg/kg only without renal toxicity. Stop at cumulative 4 mg/kg or BUN above 50 mg/dL. Ketoconazole 10 mg/kg PO every 12 hours for at least 60 days. |
Horses
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Systemic mycosis | 0.3 mg/kg | IV | Printed course: day 1 followed by 3 consecutive days, then repeat after a 24–48-hour drug-free interval. The wording does not unambiguously define the number of daily doses. | |
| Fungal pneumonia – staged course | Reference only | IV | Day 1 0.3 mg/kg IV, day 2 0.4 mg/kg, day 3 0.6 mg/kg; no treatment on days 4–7, then alternate-day treatment to cumulative 6.75 mg/kg. The maintenance amount is not unambiguously restated. | |
| Pulmonary or phycomycotic infection – staged course | Reference only | IV | Day 1 0.3 mg/kg IV, day 2 0.45 mg/kg, day 3 0.6 mg/kg, then alternate-day treatment three days weekly. Dilute in 1 L D5W and infuse over 1 hour using a 16-gauge needle. Adjust for toxicity; courses described span 10–80 days. Maintenance amount is not explicit. |
Rabbit
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Systemic mycosis | 1 mg/kg | IV | Every 24 h | Conventional formulation; intensive renal monitoring. Conventional formulation only; automated preparation matching cannot distinguish conventional and lipid products. |
Llama
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Coccidioidomycosis – individual case | Reference only | IV | Single unsuccessful case, not a universal regimen: 1 mg test dose; 0.3 mg/kg IV over 4 hours followed by 3 L LRS containing B vitamins and 20 mEq KCl; later amounts increased by 10 mg every 48 hours to 1 mg/kg every 48 hours for 6 weeks. Fixed fluid and increment amounts are patient-specific. |
Bird
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Aspergillosis – intensive IV course | 1.5 mg/kg | IV | Every 8 h | Up to 3 days; Raptors and psittacines; with or followed by flucytosine. Monitor renal and marrow effects. Conventional formulation only; automated preparation matching cannot distinguish conventional and lipid products. |
| Systemic mycosis – twice-daily IV alternative | 1.5 mg/kg | IV | Every 12 h | Up to 5 days; 3–5 days. Conventional formulation only; automated preparation matching cannot distinguish conventional and lipid products. |
| Macrorhabdiasis | 100–150 mg/kg | PO | Every 12 h | Up to 30 days; Local gastrointestinal treatment; treatment failure occurs, especially with short courses. This is not systemic oral antifungal therapy. Conventional formulation only; automated preparation matching cannot distinguish conventional and lipid products. |
| Respiratory mycosis – nebulization | Reference only | INHALATION | 0.3–1 mg/mL nebulized for 15 minutes two to four times daily. Another protocol uses 1 mg/mL twice daily for 3 days; product and diluent suitability must be established. |
Indications
- Treatment of serious systemic fungal infections, including blastomycosis, histoplasmosis and coccidioidomycosis.
- Intensive initial or adjunctive antifungal treatment for severe disease, important organ involvement or inadequate response to another antifungal.
- Treatment of selected other systemic mycoses caused by susceptible fungi.
- Reported treatment of canine leishmaniasis; this is a limited and less favored veterinary application.
Contraindications
- Hypersensitivity, unless a life-threatening infection leaves no suitable alternative.
- Renal disease is a major risk requiring individualized treatment and intensive monitoring, rather than an automatic exclusion in every life-threatening infection.
- Correct dehydration, sodium depletion and electrolyte abnormalities before treatment.
Interactions
- Aminoglycosides increase renal toxicity.
- For conventional IV infusions use 5% dextrose rather than electrolyte solutions; the specifically described SC regimen uses a different diluent.
- Corticosteroids and potassium-depleting diuretics can exacerbate hypokalemia.
- Hypokalemia increases digoxin and curariform neuromuscular-blocker toxicity.
- Flucytosine may act synergistically but its toxicity can increase.
- Avoid other nephrotoxins when possible. Conventional reconstitution requires preservative-free sterile water; saline or preservative-containing diluents can precipitate the drug.
Adverse effects
- Cumulative nephrotoxicity and potassium wasting.
- Fever, phlebitis and tremors.
- Hypokalemia, hypomagnesemia and renal tubular acidosis.
- SC administration can cause sterile abscesses.
Toxicity
Conventional-course toxicity rises as cumulative exposure approaches or exceeds 6 mg/kg. Product-specific cumulative limits must be tracked.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Abelcet lipid complex 5 mg/mL 100 mg per 20 mL; lipid complex, not conventional deoxycholate or liposomal amphotericin. Formulation-specific dosing only. | Injection | 5 mg / mL | IV |
| Conventional amphotericin B reconstituted stock 5 mg/mL From a 50 mg vial plus 10 mL preservative-free sterile water; further dilution is required before IV infusion. Not a lipid formulation. | Injection | 5 mg / mL | IV |
Monitoring and Administration
Assess renal function before and during treatment, including BUN, creatinine, potassium and magnesium. Persistent azotemia can require discontinuation or change to an azole.
Pre-infusion IV saline fluid loading is described to reduce renal injury; do not confuse pretreatment saline with the dextrose drug diluent. Protect conventional infusions from light and use their formulation-specific storage conditions.
Conventional powder is supplied as a 50 mg vial; Abelcet lipid complex is 100 mg/20 mL (5 mg/mL). Do not substitute a lipid or liposomal product for conventional deoxycholate on an equal-dose assumption.
A described compounded lipid mixture contains one 50 mg vial, 40 mL sterile water and 10 mL 10% Intralipid. Reported amounts include 1–2 mg/kg for leishmaniasis, 1–2.5 mg/kg twice weekly for 8–10 treatments for other uses, and 3–3.3 mg/kg in a canine Leishmania study. Routes and formulation equivalence are insufficiently specified for generic calculation; clinical improvement did not ensure parasite clearance.
Additional lipid-associated injectable presentations are described as 50 mg and 100 mg vials, but vial content is not a final liquid concentration. Do not interchange lipid complex, cholesteryl sulfate colloidal dispersion and true liposomal preparations.
Obtain baseline renal indices, electrolytes including magnesium, urinalysis, CBC/PCV, total protein and body weight. Recheck BUN, creatinine, PCV, protein and weight before doses; monitor electrolytes and urine at least weekly. Published interruption criteria vary: BUN 30–40 mg/dL or creatinine above 3 mg/dL, whereas particular older courses use BUN above 50 mg/dL. Do not merge those thresholds into one course.
For conventional 50 mg powder, add 10 mL preservative-free sterile water and mix until clear to obtain 5 mg/mL stock. Further dilute 1:50 in 5% dextrose to 0.1 mg/mL for the specified infusion; ensure diluent pH above 4.3. An in-line filter must have pores greater than 1 micron. Store dry powder refrigerated at 2–8°C protected from light and moisture; protected reconstituted stock is stable 24 hours at room temperature or 1 week refrigerated. Do not transfer these conditions to lipid formulations.
Equine intrauterine alternative: 200–250 mg, commonly daily or every other day for 3–7 days, but supporting evidence, dilution and volume are limited. Use a separate local-administration protocol.
Avian intratracheal alternatives use 1 mg/kg one to three times daily for 3 days or every 12 hours; reptile intratracheal treatment uses 1 mg/kg daily for 14–28 treatments. Intratracheal administration is a local procedure requiring a separate treatment protocol. Conventional IV preparation compatibility must not be assumed for a saline airway preparation.
Intrathecal treatment requires a separate conventional-formulation protocol; lipid products are not interchangeable for this route. No unambiguous initial intrathecal amount is established here.